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Breast Cancer Stem Cells

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Stem Cells and Cancer

Abstract

One aspect of the analogy between embryogenesis and cancer is the emphasis on rapid cell division and self-renewal from a small number of immortal cells. A key understanding in developmental biology is the concept of determination and its consequences, in the form of lineage totipotency, pluripotency, multipotency, and unipotency. The normal cell fate decision point involves epigenetic mechanisms that are dysregulated in neoplasia. These dysregulated cell proliferation triggers are posited to specifically distinguish tumor-initiating cells from their progeny. Herein we present a review of the embryogenesis of the human breast, with an emphasis on the endocrine and epithelial–mesenchyme interactions required for proper development of tissues in the niche. We expand our conceptualization to include the relationship to the seed and soil hypothesis, and immunoediting theory. We expand on the new paradigm by explaining the relevance of side populations, plating efficiency, and tumor-initiating cells to cancer stem cell theory. Finally, we provide some suggestions for signal transduction pathway interventions, viz., that of the hedgehog/patched pathway, that might make breast cancer more amenable to specific therapeutic interventions.

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Notes

  1. 1.

    The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

References

  • Alberts, B. (2008). “Molecular biology of the cell. Reference edition.” Garland Science, New York.

    Google Scholar 

  • Al-Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J., and Clarke, M. F. (2003). Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100, 3983–8.

    PubMed  CAS  Google Scholar 

  • Alley, M. C., Scudiero, D. A., Monks, A., Hursey, M. L., Czerwinski, M. J., Fine, D. L., Abbott, B. J., Mayo, J. G., Shoemaker, R. H., and Boyd, M. R. (1988). Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res 48, 589–601.

    PubMed  CAS  Google Scholar 

  • Alonso, L., and Fuchs, E. (2003). Stem cells in the skin: waste not, Wnt not. Genes Dev 17, 1189–200.

    PubMed  CAS  Google Scholar 

  • Ameryckx, L., Leunen, M., Wylock, P., and Amy, J. J. (2005). Breast problems in children and adolescents. Eur Clin Obstet Gynaecol 1, 151–63.

    Google Scholar 

  • Athar, M., Li, C., Tang, X., Chi, S., Zhang, X., Kim, A. L., Tyring, S. K., Kopelovich, L., Hebert, J., Epstein, E. H., Jr., Bickers, D. R., and Xie, J. (2004). Inhibition of smoothened signaling prevents ultraviolet B-induced basal cell carcinomas through regulation of Fas expression and apoptosis. Cancer Res 64, 7545–52.

    PubMed  CAS  Google Scholar 

  • Auersperg, N., Wong, A. S., Choi, K. C., Kang, S. K., and Leung, P. C. (2001). Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr Rev 22, 255–88.

    PubMed  CAS  Google Scholar 

  • Bale, A. E., and Yu, K. P. (2001). The hedgehog pathway and basal cell carcinomas. Hum Mol Genet 10, 757–62.

    PubMed  CAS  Google Scholar 

  • Bapat, S. A. (2007). Evolution of cancer stem cells. Semin Cancer Biol 17, 204–13.

    PubMed  CAS  Google Scholar 

  • Barnhart, B. C., and Simon, M. C. (2007). Metastasis and stem cell pathways. Cancer Metastasis Rev 26, 261–71.

    PubMed  CAS  Google Scholar 

  • Bates, S. E., Mickley, L. A., Chen, Y. N., Richert, N., Rudick, J., Biedler, J. L., and Fojo, A. T. (1989). Expression of a drug resistance gene in human neuroblastoma cell lines: modulation by retinoic acid-induced differentiation. Mol Cell Biol 9, 4337–44.

    PubMed  CAS  Google Scholar 

  • Beachy, P. A., Karhadkar, S. S., and Berman, D. M. (2004). Tissue repair and stem cell renewal in carcinogenesis. Nature 432, 324–31.

    PubMed  CAS  Google Scholar 

  • Bengochea, A., de Souza, M. M., Lefrancois, L., Le Roux, E., Galy, O., Chemin, I., Kim, M., Wands, J. R., Trepo, C., Hainaut, P., Scoazec, J. Y., Vitvitski, L., and Merle, P. (2008). Common dysregulation of Wnt/Frizzled receptor elements in human hepatocellular carcinoma. Br J Cancer 99, 143–50.

    PubMed  CAS  Google Scholar 

  • Ben-Porath, I., Thomson, M. W., Carey, V. J., Ge, R., Bell, G. W., Regev, A., and Weinberg, R. A. (2008). An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 40, 499–507.

    PubMed  CAS  Google Scholar 

  • Berman, D. M., Karhadkar, S. S., Maitra, A., Montes De Oca, R., Gerstenblith, M. R., Briggs, K., Parker, A. R., Shimada, Y., Eshleman, J. R., Watkins, D. N., and Beachy, P. A. (2003). Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature 425, 846–51.

    PubMed  CAS  Google Scholar 

  • Bijlsma, M. F., Spek, C. A., Zivkovic, D., van de Water, S., Rezaee, F., and Peppelenbosch, M. P. (2006). Repression of smoothened by patched-dependent (pro-)vitamin D3 secretion. PLoS Biol 4, e232.

    PubMed  Google Scholar 

  • Bjerknes, M. (1996). Expansion of mutant stem cell populations in the human colon. J Theor Biol 178, 381–5.

    PubMed  CAS  Google Scholar 

  • Black, R. F., Jarman, L., and Simpson, J. (1998). “Lactation specialist self-study series.” Jones and Bartlett, Sudbury, MA.

    Google Scholar 

  • Blanpain, C., Horsley, V., and Fuchs, E. (2007). Epithelial stem cells: turning over new leaves. Cell 128, 445–58.

    PubMed  CAS  Google Scholar 

  • Brinster, R. L. (1976). Participation of teratocarcinoma cells in mouse embryo development. Cancer Res 36, 3412–4.

    PubMed  CAS  Google Scholar 

  • Brinton, R. D. (2001). Cellular and molecular mechanisms of estrogen regulation of memory function and neuroprotection against Alzheimer's disease: recent insights and remaining challenges. Learn Mem 8, 121–33.

    PubMed  CAS  Google Scholar 

  • Buhimschi, C. S. (2004). Endocrinology of lactation. Obstet Gynecol Clin North Am 31, 963–79, xii.

    PubMed  Google Scholar 

  • Castagna, M., Takai, Y., Kaibuchi, K., Sano, K., Kikkawa, U., and Nishizuka, Y. (1982). Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem 257, 7847–51.

    PubMed  CAS  Google Scholar 

  • Chen, J. K., Taipale, J., Young, K. E., Maiti, T., and Beachy, P. A. (2002). Small molecule modulation of Smoothened activity. Proc Natl Acad Sci USA 99, 14071–6.

    PubMed  CAS  Google Scholar 

  • Chidambaram, A., Goldstein, A. M., Gailani, M. R., Gerrard, B., Bale, S. J., DiGiovanna, J. J., Bale, A. E., and Dean, M. (1996). Mutations in the human homolog of the Drosophila patched gene in Caucasian and African American nevoid basal cell carcinoma syndrome patients. Cancer Res. 56, 4599–601.

    PubMed  CAS  Google Scholar 

  • Chlebowski, R. T. (2005). Obesity and early-stage breast cancer. J Clin Oncol 23, 1345–7.

    PubMed  Google Scholar 

  • Chung, L. W., Baseman, A., Assikis, V., and Zhau, H. E. (2005). Molecular insights into prostate cancer progression: the missing link of tumor microenvironment. J Urol 173, 10–20.

    PubMed  Google Scholar 

  • Clarke, R. B. (2003). Steroid receptors and proliferation in the human breast. Steroids 68, 789–94.

    PubMed  CAS  Google Scholar 

  • Cooper, A. (1840). “On the anatomy of the breast.” Longman, Orme, Green, Brown, and Longmans, London.

    Google Scholar 

  • Crawford, N. P., and Hunter, K. W. (2006). New perspectives on hereditary influences in metastatic progression. Trends Genet 22, 555–61.

    PubMed  CAS  Google Scholar 

  • Creasy, R. K., Resnik, R., and Iams, J. D. (2004). “Maternal–fetal medicine : principles and practice.” Saunders, Philadelphia, PA.

    Google Scholar 

  • Dean, M. (1997). Towards a unified model of tumor suppression: lessons learned from the human patched gene. Biochim Biophys Acta 1332, M43–52.

    PubMed  CAS  Google Scholar 

  • Dean, M., and Annilo, T. (2005). Evolution of the ATP-binding cassette (ABC) transporter superfamily in vertebrates. Annu Rev Genom Hum Genet 6, 123–42.

    CAS  Google Scholar 

  • Dean, M., Fojo, T., and Bates, S. (2005). Tumour stem cells and drug resistance. Nat Rev Cancer 5, 275–84.

    PubMed  CAS  Google Scholar 

  • Deroo, B. J., and Korach, K. S. (2006). Estrogen receptors and human disease. J Clin Invest 116, 561–70.

    PubMed  CAS  Google Scholar 

  • Deschner, E. E., and Lipkin, M. (1975). Proliferative patterns in colonic mucosa in familial polyposis. Cancer 35, 413–8.

    PubMed  CAS  Google Scholar 

  • Deugnier, M. A., Faraldo, M. M., Janji, B., Rousselle, P., Thiery, J. P., and Glukhova, M. A. (2002). EGF controls the in vivo developmental potential of a mammary epithelial cell line possessing progenitor properties. J Cell Biol 159, 453–63.

    PubMed  CAS  Google Scholar 

  • Do, J. T., Han, D. W., and Scholer, H. R. (2006). Reprogramming somatic gene activity by fusion with pluripotent cells. Stem Cell Rev 2, 257–64.

    PubMed  CAS  Google Scholar 

  • Dontu, G., Al-Hajj, M., Abdallah, W. M., Clarke, M. F., and Wicha, M. S. (2003). Stem cells in normal breast development and breast cancer. Cell Prolif 36 Suppl 1, 59–72.

    PubMed  Google Scholar 

  • Dunn, G. P., Old, L. J., and Schreiber, R. D. (2004a). The immunobiology of cancer immunosurveillance and immunoediting. Immunity 21, 137–48.

    PubMed  CAS  Google Scholar 

  • Dunn, G. P., Old, L. J., and Schreiber, R. D. (2004b). The three Es of cancer immunoediting. Annu Rev Immunol 22, 329–60.

    PubMed  CAS  Google Scholar 

  • Eaden, J. (2004). Review article: colorectal carcinoma and inflammatory bowel disease. Alim Pharmacol Ther 20 Suppl 4, 24–30.

    Google Scholar 

  • Eccles, S. A., and Welch, D. R. (2007). Metastasis: recent discoveries and novel treatment strategies. Lancet 369, 1742–57.

    PubMed  CAS  Google Scholar 

  • Elenbaas, B., Spirio, L., Koerner, F., Fleming, M. D., Zimonjic, D. B., Donaher, J. L., Popescu, N. C., Hahn, W. C., and Weinberg, R. A. (2001). Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells. Genes Dev 15, 50–65.

    PubMed  CAS  Google Scholar 

  • Fan, X., Matsui, W., Khaki, L., Stearns, D., Chun, J., Li, Y. M., and Eberhart, C. G. (2006). Notch pathway inhibition depletes stem-like cells and blocks engraftment in embryonal brain tumors. Cancer Res 66, 7445–52.

    PubMed  CAS  Google Scholar 

  • Folkman, J. (2002). Role of angiogenesis in tumor growth and metastasis. Semin Oncol 29, 15–8.

    PubMed  CAS  Google Scholar 

  • Fuchs, E. (1882). Das Sarkom des Uvealtractus. Graefe's Arch Ophthalmol XII, 233.

    Google Scholar 

  • Gail, M. H., Brinton, L. A., Byar, D. P., Corle, D. K., Green, S. B., Schairer, C., and Mulvihill, J. J. (1989). Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst 81, 1879–86.

    PubMed  CAS  Google Scholar 

  • Gailani, M. R., Stahle-Backdahl, M., Leffell, D. J., Glynn, M., Zaphiropoulos, P. G., Pressman, C., Unden, A. B., Dean, M., Brash, D. E., Bale, A. E., and Toftgard, R. (1996). The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. Nat Genet 14, 78–81.

    PubMed  CAS  Google Scholar 

  • Gardner, E. J. (1962). Follow-up study of a family group exhibiting dominant inheritance for a syndrome including intestinal polyps, osteomas, fibromas and epidermal cysts. Am J Hum Genet 14, 376–90.

    PubMed  CAS  Google Scholar 

  • Gilbert, S. F., Singer, S. R., Tyler, M. S., and Kozlowski, R. N. (2006). “Developmental biology.” Sinauer Associates, Sunderland, MA.

    Google Scholar 

  • Goodell, M. A., Brose, K., Paradis, G., Conner, A. S., and Mulligan, R. C. (1996). Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 183, 1797–806.

    PubMed  CAS  Google Scholar 

  • Gottesman, M. M., Fojo, T., and Bates, S. E. (2002). Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2, 48–58.

    PubMed  CAS  Google Scholar 

  • Groden, J., et al. (1991). Identification and characterization of the familial adenomatous polyposis coli gene. Cell 66, 589–600.

    PubMed  CAS  Google Scholar 

  • Gupta, G. P., and Massague, J. (2006). Cancer metastasis: building a framework. Cell 127, 679–95.

    PubMed  CAS  Google Scholar 

  • Hahn, H., Christiansen, J., Wicking, C., Zaphiropoulos, P. G., Chidambaram, A., Gerrard, B., Vorechovsky, I., Bale, A. E., Toftgard, R., Dean, M., and Wainwright, B. (1996a). A mammalian patched homolog is expressed in target tissues of sonic hedgehog and maps to a region associated with developmental anomalies. J Biol Chem 271, 12125–8.

    PubMed  CAS  Google Scholar 

  • Hahn, H., Wicking, C., Zaphiropoulous, P. G., Gailani, M. R., Shanley, S., Chidambaram, A., Vorechovsky, I., Holmberg, E., Unden, A. B., Gillies, S., Negus, K., Smyth, I., Pressman, C., Leffell, D. J., Gerrard, B., Goldstein, A. M., Dean, M., Toftgard, R., Chenevix-Trench, G., Wainwright, B., and Bale, A. E. (1996b). Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 85, 841–51.

    PubMed  CAS  Google Scholar 

  • Hall, J. G. (2003). Twinning. Lancet 362, 735–43.

    PubMed  Google Scholar 

  • Hamburger, A. W., and Salmon, S. E. (1977). Primary bioassay of human tumor stem cells. Science 197, 461–3.

    PubMed  CAS  Google Scholar 

  • Harrison, R. F., and Biswas, S. (1980). Maternal plasma, human placental lactogen, alpha-fetoprotein, prolactin and growth hormone in early pregnancy. Int J Gynaecol Obstet 17, 471–6.

    PubMed  CAS  Google Scholar 

  • Hemmati, H. D., Nakano, I., Lazareff, J. A., Masterman-Smith, M., Geschwind, D. H., Bronner-Fraser, M., and Kornblum, H. I. (2003). Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci USA 100, 15178–83.

    PubMed  CAS  Google Scholar 

  • Hennings, H., and Boutwell, R. K. (1970). Studies on the mechanism of skin tumor promotion. Cancer Res 30, 312–20.

    PubMed  CAS  Google Scholar 

  • Henrich, C. J., Bokesch, H. R., Dean, M., Bates, S. E., Robey, R. W., Goncharova, E. I., Wilson, J. A., and McMahon, J. B. (2006). A high-throughput cell-based assay for inhibitors of ABCG2 activity. J Biomol Screen 11, 176–83.

    PubMed  CAS  Google Scholar 

  • Hewitt, R. E., McMarlin, A., Kleiner, D., Wersto, R., Martin, P., Tsokos, M., Stamp, G. W., and Stetler-Stevenson, W. G. (2000). Validation of a model of colon cancer progression. J Pathol 192, 446–54.

    PubMed  CAS  Google Scholar 

  • Hirschmann-Jax, C., Foster, A. E., Wulf, G. G., Nuchtern, J. G., Jax, T. W., Gobel, U., Goodell, M. A., and Brenner, M. K. (2004). A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA 101, 14228–33.

    PubMed  CAS  Google Scholar 

  • Ho, K. J., and Liao, J. K. (2002). Nonnuclear actions of estrogen. Arterioscler Thromb Vasc Biol 22, 1952–61.

    PubMed  CAS  Google Scholar 

  • Houghton, P. J., Germain, G. S., Harwood, F. C., Schuetz, J. D., Stewart, C. F., Buchdunger, E., and Traxler, P. (2004). Imatinib mesylate is a potent inhibitor of the ABCG2 (BCRP) transporter and reverses resistance to topotecan and SN-38 in vitro. Cancer Res 64, 2333–7.

    PubMed  CAS  Google Scholar 

  • Huang, X., Cho, S., and Spangrude, G. J. (2007). Hematopoietic stem cells: generation and self-renewal. Cell Death Differ 14, 1851–9.

    PubMed  CAS  Google Scholar 

  • Ince, T. A., Richardson, A. L., Bell, G. W., Saitoh, M., Godar, S., Karnoub, A. E., Iglehart, J. D., and Weinberg, R. A. (2007). Transformation of different human breast epithelial cell types leads to distinct tumor phenotypes. Cancer Cell 12, 160–70.

    PubMed  CAS  Google Scholar 

  • Jaenisch, R., Hochedlinger, K., Blelloch, R., Yamada, Y., Baldwin, K., and Eggan, K. (2004). Nuclear cloning, epigenetic reprogramming, and cellular differentiation. Cold Spring Harb Symp Quant Biol 69, 19–27.

    PubMed  CAS  Google Scholar 

  • James, L. F., Panter, K. E., Gaffield, W., and Molyneux, R. J. (2004). Biomedical applications of poisonous plant research. J Agric Food Chem 52, 3211–30.

    PubMed  CAS  Google Scholar 

  • Jilka, R. L. (1998). Cytokines, bone remodeling, and estrogen deficiency: a 1998 update. Bone 23, 75–81.

    PubMed  CAS  Google Scholar 

  • Johnson, R. L., Rothman, A. L., Xie, J., Goodrich, L. V., Bare, J. W., Bonifas, J. M., Quinn, A. G., Myers, R. M., Cox, D. R., Epstein, E. H., Jr., and Scott, M. P. (1996). Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science 272, 1668–71.

    PubMed  CAS  Google Scholar 

  • Jordan, V. C., and Morrow, M. (1999). Tamoxifen, raloxifene, and the prevention of breast cancer. Endocr Rev 20, 253–78.

    PubMed  CAS  Google Scholar 

  • Karhadkar, S. S., Bova, G. S., Abdallah, N., Dhara, S., Gardner, D., Maitra, A., Isaacs, J. T., Berman, D. M., and Beachy, P. A. (2004). Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature 431, 707–12.

    PubMed  CAS  Google Scholar 

  • Karpinets, T. V., and Foy, B. D. (2005). Tumorigenesis: the adaptation of mammalian cells to sustained stress environment by epigenetic alterations and succeeding matched mutations. Carcinogenesis 26, 1323–34.

    PubMed  CAS  Google Scholar 

  • Kasemeier-Kulesa, J. C., Teddy, J. M., Postovit, L. M., Seftor, E. A., Seftor, R. E., Hendrix, M. J., and Kulesa, P. M. (2008). Reprogramming multipotent tumor cells with the embryonic neural crest microenvironment. Dev Dyn 237, 2657–2666.

    Google Scholar 

  • Kauff, N. D., Satagopan, J. M., Robson, M. E., Scheuer, L., Hensley, M., Hudis, C. A., Ellis, N. A., Boyd, J., Borgen, P. I., Barakat, R. R., Norton, L., Castiel, M., Nafa, K., and Offit, K. (2002). Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 346, 1609–15.

    PubMed  Google Scholar 

  • Kim, M., Turnquist, H., Jackson, J., Sgagias, M., Yan, Y., Gong, M., Dean, M., Sharp, J. G., and Cowan, K. (2002). The multidrug resistance transporter ABCG2 (breast cancer resistance protein 1) effluxes Hoechst 33342 and is overexpressed in hematopoietic stem cells. Clin Cancer Res 8, 22–8.

    PubMed  CAS  Google Scholar 

  • Kimball, J. W. (2003). Kimball's biology pages. John W. Kimball [Andover, MA].

    Google Scholar 

  • Kinzler, K. W., and Vogelstein, B. (1996). Lessons from hereditary colorectal cancer. Cell 87, 159–70.

    PubMed  CAS  Google Scholar 

  • Knudson, A. G., Jr. (1971). Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 68, 820–3.

    PubMed  Google Scholar 

  • Knudson, A. G. (1993). Antioncogenes and human cancer. Proc Natl Acad Sci USA 90, 10914–21.

    PubMed  CAS  Google Scholar 

  • Kondo, T., Setoguchi, T., and Taga, T. (2004). Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci USA 101, 781–6.

    PubMed  CAS  Google Scholar 

  • Kuperwasser, C., Chavarria, T., Wu, M., Magrane, G., Gray, J. W., Carey, L., Richardson, A., and Weinberg, R. A. (2004). Reconstruction of functionally normal and malignant human breast tissues in mice. Proc Natl Acad Sci USA 101, 4966–71.

    PubMed  CAS  Google Scholar 

  • LaBarge, M. A., Petersen, O. W., and Bissell, M. J. (2007). Of microenvironments and mammary stem cells. Stem Cell Rev 3, 137–46.

    PubMed  CAS  Google Scholar 

  • Lagasse, E., Connors, H., Al-Dhalimy, M., Reitsma, M., Dohse, M., Osborne, L., Wang, X., Finegold, M., Weissman, I. L., and Grompe, M. (2000). Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 6, 1229–34.

    PubMed  CAS  Google Scholar 

  • Langley, R. R., and Fidler, I. J. (2007). Tumor cell-organ microenvironment interactions in the pathogenesis of cancer metastasis. Endocr Rev 28, 297–321.

    PubMed  CAS  Google Scholar 

  • Lapidot, T., Sirard, C., Vormoor, J., Murdoch, B., Hoang, T., Caceres-Cortes, J., Minden, M., Paterson, B., Caligiuri, M. A., and Dick, J. E. (1994). A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367, 645–8.

    PubMed  CAS  Google Scholar 

  • Lawrence, R. A., and Lawrence, R. A. (1985). “Breastfeeding, a guide for the medical profession.” Mosby, St. Louis.

    Google Scholar 

  • Leri, A., Kajstura, J., and Anversa, P. (2005). Cardiac stem cells and mechanisms of myocardial regeneration. Physiol Rev 85, 1373–416.

    PubMed  CAS  Google Scholar 

  • Leslie, K. K., and Lange, C. A. (2005). Breast cancer and pregnancy. Obstet Gynecol Clin North Am 32, 547–58.

    PubMed  Google Scholar 

  • Lou, H., and Dean, M. (2007). Targeted therapy for cancer stem cells: the patched pathway and ABC transporters. Oncogene 26, 1357–60.

    PubMed  CAS  Google Scholar 

  • McCullough, L. D., Alkayed, N. J., Traystman, R. J., Williams, M. J., and Hurn, P. D. (2001). Postischemic estrogen reduces hypoperfusion and secondary ischemia after experimental stroke. Stroke 32, 796–802.

    PubMed  CAS  Google Scholar 

  • McKenzie, J. L., Gan, O. I., Doedens, M., Wang, J. C., and Dick, J. E. (2006). Individual stem cells with highly variable proliferation and self-renewal properties comprise the human hematopoietic stem cell compartment. Nat Immunol 7, 1225–33.

    PubMed  CAS  Google Scholar 

  • McLachlan, J. A. (2001). Environmental signaling: what embryos and evolution teach us about endocrine disrupting chemicals. Endocr Rev 22, 319–41.

    PubMed  CAS  Google Scholar 

  • Michalopoulos, G. K. (2007). Liver regeneration. J Cell Physiol 213, 286–300.

    PubMed  CAS  Google Scholar 

  • Mickley, L. A., Bates, S. E., Richert, N. D., Currier, S., Tanaka, S., Foss, F., Rosen, N., and Fojo, A. T. (1989). Modulation of the expression of a multidrug resistance gene (mdr-1/P-glycoprotein) by differentiating agents. J Biol Chem 264, 18031–40.

    PubMed  CAS  Google Scholar 

  • Mintz, B., and Illmensee, K. (1975). Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc Natl Acad Sci USA 72, 3585–9.

    PubMed  Google Scholar 

  • Mizoguchi, T., Yamada, K., Furukawa, T., Hidaka, K., Hisatsugu, T., Shimazu, H., Tsuruo, T., Sumizawa, T., and Akiyama, S. (1990). Expression of the MDR1 gene in human gastric and colorectal carcinomas. J Natl Cancer Inst 82, 1679–83.

    PubMed  CAS  Google Scholar 

  • Moore, K. L., Persaud, T. V. N., Moore, K. L., and Moore, K. L. (1993). “Study guide and review manual of human embryology.” Saunders, Philadelphia.

    Google Scholar 

  • Morrison, S. J., Shah, N. M., and Anderson, D. J. (1997). Regulatory mechanisms in stem cell biology. Cell 88, 287–98.

    PubMed  CAS  Google Scholar 

  • Moser, A. R., Dove, W. F., Roth, K. A., and Gordon, J. I. (1992). The Min (multiple intestinal neoplasia) mutation: its effect on gut epithelial cell differentiation and interaction with a modifier system. J Cell Biol 116, 1517–26.

    PubMed  CAS  Google Scholar 

  • Muller, A., Homey, B., Soto, H., Ge, N., Catron, D., Buchanan, M. E., McClanahan, T., Murphy, E., Yuan, W., Wagner, S. N., Barrera, J. L., Mohar, A., Verastegui, E., and Zlotnik, A. (2001). Involvement of chemokine receptors in breast cancer metastasis. Nature 410, 50–6.

    PubMed  CAS  Google Scholar 

  • Murphy, P. M. (2001). Chemokines and the molecular basis of cancer metastasis. N Engl J Med 345, 833–5.

    PubMed  CAS  Google Scholar 

  • Nakachi, K., Hayashi, T., Imai, K., and Kusunoki, Y. (2004). Perspectives on cancer immuno-epidemiology. Cancer Sci 95, 921–9.

    PubMed  CAS  Google Scholar 

  • Nishisho, I., Nakamura, Y., Miyoshi, Y., Miki, Y., Ando, H., Horii, A., Koyama, K., Utsunomiya, J., Baba, S., and Hedge, P. (1991). Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 253, 665–9.

    PubMed  CAS  Google Scholar 

  • Nishiyama, K., Shirahama, T., Yoshimura, A., Sumizawa, T., Furukawa, T., Ichikawa-Haraguchi, M., Akiyama, S., and Ohi, Y. (1993). Expression of the multidrug transporter, P-glycoprotein, in renal and transitional cell carcinomas. Cancer 71, 3611–9.

    PubMed  CAS  Google Scholar 

  • Norbury, R., Cutter, W. J., Compton, J., Robertson, D. M., Craig, M., Whitehead, M., and Murphy, D. G. (2003). The neuroprotective effects of estrogen on the aging brain. Exp Gerontol 38, 109–17.

    PubMed  CAS  Google Scholar 

  • Novaro, V., Roskelley, C. D., and Bissell, M. J. (2003). Collagen-IV and laminin-1 regulate estrogen receptor alpha expression and function in mouse mammary epithelial cells. J Cell Sci 116, 2975–86.

    PubMed  CAS  Google Scholar 

  • Novaro, V., Radisky, D. C., Ramos Castro, N. E., Weisz, A., and Bissell, M. J. (2004). Malignant mammary cells acquire independence from extracellular context for regulation of estrogen receptor alpha. Clin Cancer Res 10, 402S–9S.

    PubMed  CAS  Google Scholar 

  • Nusslein-Volhard, C., and Wieschaus, E. (1980). Mutations affecting segment number and polarity in Drosophila. Nature 287, 795–801.

    PubMed  CAS  Google Scholar 

  • Paget, S. (1889). The distribution of secondary growths in cancer of the breast. Lancet 133, 571–3.

    Google Scholar 

  • Parmar, H., and Cunha, G. R. (2004). Epithelial–stromal interactions in the mouse and human mammary gland in vivo. Endocr Relat Cancer 11, 437–58.

    PubMed  CAS  Google Scholar 

  • Potten, C. S. (1991). Regeneration in epithelial proliferative units as exemplified by small intestinal crypts. CIBA Found Symp 160, 54–71; discussion 71–6.

    PubMed  CAS  Google Scholar 

  • Raff, M. (2003). Adult stem cell plasticity: fact or artifact? Annu Rev Cell Dev Biol 19, 1–22.

    PubMed  CAS  Google Scholar 

  • Rajaraman, R., Guernsey, D. L., Rajaraman, M. M., and Rajaraman, S. R. (2006). Stem cells, senescence, neosis and self-renewal in cancer. Cancer Cell Int 6, 25.

    PubMed  Google Scholar 

  • Rakoff-Nahoum, S. (2006). Why cancer and inflammation? Yale J Biol Med 79, 123–30.

    PubMed  CAS  Google Scholar 

  • Reya, T., Morrison, S. J., Clarke, M. F., and Weissman, I. L. (2001). Stem cells, cancer, and cancer stem cells. Nature 414, 105–11.

    PubMed  CAS  Google Scholar 

  • Riordan, J. (2005). “Breastfeeding and human lactation.” Jones and Bartlett, Sudbury, MA.

    Google Scholar 

  • Rossouw, J. E. (2000). Debate: The potential role of estrogen in the prevention of heart disease in women after menopause. Curr Control Trials Cardiovasc Med 1, 135–8.

    PubMed  CAS  Google Scholar 

  • Rous, P. (1966). The challenge to man of the neoplastic cell. In “Nobel Lectures”, pp. v. Published for the Nobel Foundation by Elsevier, Amsterdam, NY.

    Google Scholar 

  • Rous, P., and Kidd, J. G. (1941). Conditional neoplasms and sub-threshold states. A study of the tar tumours of rabbits. J Exp Med 73, 365–89.

    PubMed  CAS  Google Scholar 

  • Scharenberg, C. W., Harkey, M. A., and Torok-Storb, B. (2002). The ABCG2 transporter is an efficient Hoechst 33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors. Blood 99, 507–12.

    PubMed  CAS  Google Scholar 

  • Schatton, T., and Frank, M. H. (2008). Cancer stem cells and human malignant melanoma. Pigment Cell Melanoma Res 21, 39–55.

    PubMed  CAS  Google Scholar 

  • Schlessinger, D., and Van Zant, G. (2001). Does functional depletion of stem cells drive aging? Mech Ageing Dev 122, 1537–53.

    PubMed  CAS  Google Scholar 

  • Seydoux, G., and Braun, R. E. (2006). Pathway to totipotency: lessons from germ cells. Cell 127, 891–904.

    PubMed  CAS  Google Scholar 

  • Shankaran, V., Ikeda, H., Bruce, A. T., White, J. M., Swanson, P. E., Old, L. J., and Schreiber, R. D. (2001). IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410, 1107–11.

    PubMed  CAS  Google Scholar 

  • Shipitsin, M., and Polyak, K. (2008). The cancer stem cell hypothesis: in search of definitions, markers, and relevance. Lab Invest 88, 459–63.

    PubMed  CAS  Google Scholar 

  • Shubik, P. (2002). Reflections on the implications of multistage carcinogenesis for the nature of neoplasia. Food Chem Toxicol 40, 739–42.

    PubMed  CAS  Google Scholar 

  • Smith, G. H. (2006). Mammary stem cells come of age, prospectively. Trends Mol Med 12, 287–9.

    PubMed  CAS  Google Scholar 

  • Smith, G. H., and Boulanger, C. A. (2002). Mammary stem cell repertoire: new insights in aging epithelial populations. Mech Ageing Dev 123, 1505–19.

    PubMed  CAS  Google Scholar 

  • Spemann, H. (1918). Über die Determination der ersten Organanlagen des Amphibienembryonen. Zool Jahr Suppl 15, 1–48.

    Google Scholar 

  • Sternlicht, M. D. (2006). Key stages in mammary gland development: the cues that regulate ductal branching morphogenesis. Breast Cancer Res 8, 201.

    PubMed  Google Scholar 

  • Stetler-Stevenson, W. G. (2001). The role of matrix metalloproteinases in tumor invasion, metastasis, and angiogenesis. Surg Oncol Clin North Am 10, 383–92, x.

    CAS  Google Scholar 

  • Stevenson, R. E., and Hall, J. G. (2006). “Human malformations and related anomalies.” Oxford University Press, Oxford.

    Google Scholar 

  • Strieter, R. M. (2001). Chemokines: not just leukocyte chemoattractants in the promotion of cancer. Nat Immunol 2, 285–6.

    PubMed  CAS  Google Scholar 

  • Su, L. K., Kinzler, K. W., Vogelstein, B., Preisinger, A. C., Moser, A. R., Luongo, C., Gould, K. A., and Dove, W. F. (1992). Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science 256, 668–70.

    PubMed  CAS  Google Scholar 

  • Teicher, B. A. (1994). Hypoxia and drug resistance. Cancer Metastasis Rev 13, 139–68.

    PubMed  CAS  Google Scholar 

  • Tennant, R. (1999). What is a tumor promoter? Environ Health Perspect 107, A390–1.

    Google Scholar 

  • Thayer, S. P., di Magliano, M. P., Heiser, P. W., Nielsen, C. M., Roberts, D. J., Lauwers, G. Y., Qi, Y. P., Gysin, S., Fernandez-del Castillo, C., Yajnik, V., Antoniu, B., McMahon, M., Warshaw, A. L., and Hebrok, M. (2003). Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature 425, 851–6.

    PubMed  CAS  Google Scholar 

  • Thomlinson, R. H., and Gray, L. H. (1955). The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer 9, 539–49.

    PubMed  CAS  Google Scholar 

  • Till, J. E., McCulloch, E. A., and Siminovitch, L. (1964). A stochastic model of stem cell proliferation, based on the growth of spleen colony-forming cells. Proc Natl Acad Sci USA 51, 29–36.

    PubMed  CAS  Google Scholar 

  • Tostar, U., Malm, C.J., Meis-Kindblom, J.M., Kindblom, L. G., Toftgard, R., and Unden, A. B. (2006). Deregulation of the hedgehog signalling pathway: a possible role for the PTCH and SUFU genes in human rhabdomyoma and rhabdomyosarcoma development. J Pathol 208, 17–25.

    Google Scholar 

  • Trichopoulos, D., Lagiou, P., and Adami, H. O. (2005). Towards an integrated model for breast cancer etiology: the crucial role of the number of mammary tissue-specific stem cells. Breast Cancer Res 7, 13–7.

    PubMed  Google Scholar 

  • Trosko, J. E. (2005). The role of stem cells and cell-cell communication in radiation carcinogenesis: ignored concepts. BJR Suppl 27, 132–8.

    PubMed  CAS  Google Scholar 

  • Trosko, J. E., and Tai, M. H. (2006). Adult stem cell theory of the multi-stage, multi-mechanism theory of carcinogenesis: role of inflammation on the promotion of initiated stem cells. Contrib Microbiol 13, 45–65.

    PubMed  Google Scholar 

  • Tsonis, P. A. (2007). Bridging knowledge gaps on the long road to regeneration: classical models meet stem cell manipulation and bioengineering. Mol Interv 7, 249–50.

    PubMed  Google Scholar 

  • Vogelstein, B., and Kinzler, K. W. (1993). The multistep nature of cancer. Trends Genet 9, 138–41.

    PubMed  CAS  Google Scholar 

  • Vona-Davis, L., and Rose, D. P. (2007). Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression. Endocr Relat Cancer 14, 189–206.

    PubMed  CAS  Google Scholar 

  • Waddington, C. H. (1966). “Principles of development and differentiation.” Macmillan, London.

    Google Scholar 

  • Ward, R. J., and Dirks, P. B. (2007). Cancer stem cells: at the headwaters of tumor development. Annu Rev Pathol 2, 175–89.

    PubMed  CAS  Google Scholar 

  • Watkins, D. N., Berman, D. M., Burkholder, S. G., Wang, B., Beachy, P. A., and Baylin, S. B. (2003). Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature 422, 313–7.

    PubMed  CAS  Google Scholar 

  • Xiao, Y., Ye, Y., Yearsley, K., Jones, S., and Barsky, S. H. (2008). The lymphovascular embolus of inflammatory breast cancer expresses a stem cell-like phenotype. Am J Pathol 173, 561–74.

    PubMed  CAS  Google Scholar 

  • Zhai, P., Eurell, T. E., Cooke, P. S., Lubahn, D. B., and Gross, D. R. (2000a). Myocardial ischemia-reperfusion injury in estrogen receptor-alpha knockout and wild-type mice. Am J Physiol Heart Circ Physiol 278, H1640–7.

    Google Scholar 

  • Zhai, P., Eurell, T. E., Cotthaus, R., Jeffery, E. H., Bahr, J. M., and Gross, D. R. (2000b). Effect of estrogen on global myocardial ischemia-reperfusion injury in female rats. Am J Physiol Heart Circ Physiol 279, H2766–75.

    Google Scholar 

  • Zhou, S., Schuetz, J. D., Bunting, K. D., Colapietro, A. M., Sampath, J., Morris, J. J., Lagutina, I., Grosveld, G. C., Osawa, M., Nakauchi, H., and Sorrentino, B. P. (2001). The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med 7, 1028–34.

    PubMed  CAS  Google Scholar 

  • Zhou, S., Morris, J. J., Barnes, Y., Lan, L., Schuetz, J. D., and Sorrentino, B. P. (2002). Bcrp1 gene expression is required for normal numbers of side population stem cells in mice, and confers relative protection to mitoxantrone in hematopoietic cells in vivo. Proc Natl Acad Sci USA 99, 12339–44.

    PubMed  CAS  Google Scholar 

  • Zimonjic, D., Brooks, M. W., Popescu, N., Weinberg, R. A., and Hahn, W. C. (2001). Derivation of human tumor cells in vitro without widespread genomic instability. Cancer Res 61, 8838–44.

    PubMed  CAS  Google Scholar 

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Acknowledgments

The authors wish to thank Dr. Jodie Fleming of NCI, for her helpful comments on this chapter. This chapter has been funded in whole or in part with Federal Funds from the Center for Cancer Research, National Cancer Institute and the National Institutes of Health.

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  1. Human Genetics Section, Laboratory of Experimental Immunology, Cancer Inflammation Program, Center for Cancer Research, NCI-Frederick, Frederick, MD 21703, USA

    Bert Gold & Michael Dean

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    Gold, B., Dean, M. (2009). Breast Cancer Stem Cells. In: Majumder, S. (eds) Stem Cells and Cancer. Springer, New York, NY. https://doi.org/10.1007/978-0-387-89611-3_7

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