Skip to main content

Advertisement

SpringerLink
Log in

Nestin involvement in tissue injury and cancer - a potential tumor marker?

  • Review
  • Published:
Cellular Oncology Aims and scope Submit manuscript

Abstract

Background

In eukaryotic cells, the cytoskeleton contains three major filamentous components: actin microfilaments, microtubules and intermediate filaments. Nestin represents one of the class VI intermediate filament proteins. Clinical and molecular analyses have revealed substantial information regarding the presence of Nestin in cells with progenitor or stem cell properties. During tissue injury Nestin is expressed in cells with progenitor cell-like properties. These cells may serve as a tissue reserve and, as such, may contribute to tissue repair. Based on currently available data, Nestin also appears to be implicated in two oncogenic processes. First, Nestin has been found to be expressed in cancer stem-like cells and poorly differentiated cancer cells and, as such, Nestin is thought to contribute to the aggressive behavior of these cells. Second, Nestin has been found to be involved in tumor angiogenesis through an interaction of cancer cells and blood vessel endothelial cells and, as such, Nestin is thought to facilitate tumor growth.

Conclusions

We conclude that Nestin may serve as a promising tumor marker and as a potential therapeutic target amenable to tumor suppression and angiogenesis inhibition.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. L. Chang, R.D. Goldman, Intermediate filaments mediate cytoskeletal crosstalk. Nat. Rev. Mol. Cell Biol. 5, 601–13 (2004)

    Article  PubMed  CAS  Google Scholar 

  2. U. Lendahl, L.B. Zimmerman, R.D. McKay, CNS stem cells express a new class of intermediate filament protein. Cell 60, 585–95 (1990)

    Article  PubMed  CAS  Google Scholar 

  3. M.J. Marvin, J. Dahlstrand, U. Lendahl, R.D. McKay, A rod end deletion in the intermediate filament protein nestin alters its subcellular localization in neuroepithelial cells of transgenic mice. J. Cell Sci. 111, 1951–61 (1998)

    PubMed  CAS  Google Scholar 

  4. G. Sjoberg, L. Edström, U. Lendahl, T. Sejersen, Myofibers from Duchenne/Becker muscular dystrophy and myositis express the intermediate filament nestin. J. Neuropathol. Exp. Neurol. 53, 416–23 (1994)

    Article  PubMed  CAS  Google Scholar 

  5. P.M. Steinert, Y.H. Chou, V. Prahlad, D.A. Parry, L.N. Marekov, K.C. Wu, S.I. Jang, R.D. Goldman, A high molecular weight intermediate filament-associated protein in BHK-21 cells is nestin, a type VI intermediate filament protein. Limited co-assembly in vitro to form heteropolymers with type III vimentin and type IV alpha-internexin. J. Biol. Chem. 274, 9881–90 (1990)

    Article  Google Scholar 

  6. J. Dahlstrand, L.B. Zimmerman, R.D. McKay, U. Lendahl, Characterization of the human nestin gene reveals a close evolutionary relationship to neurofilaments. J. Cell Sci. 103, 589–97 (1992)

    PubMed  CAS  Google Scholar 

  7. Z.G. Jin, L. Liu, H. Zhong, K.J. Zhang, Y.F. Chen, W. Bian, L.P. Cheng, N.H. Jing, Second intron of mouse nestin gene directs its expression in pluripotent embryonic carcinoma cells through POU factor binding site. Acta Biochim Biophys Sin (Shanghai). 38(207–12) (2006)

  8. L. Zimmerman, B. Parr, U. Lendahl, M. Cunningham, R. McKay, B. Gavin, J. Mann, G. Vassileva, A. McMahon, Independent regulatory elements in the nestin gene direct transgene expression to neural stem cells or muscle precursors. Neuron 12, 11–24 (1994)

    Article  PubMed  CAS  Google Scholar 

  9. R. Josephson, T. Müller, J. Pickel, S. Okabe, K. Reynolds, P.A. Turner, A. Zimmer, R.D. McKay, POU transcription factors control expression of CNS stem cell-specific genes. Development 125, 3087–100 (1998)

    PubMed  CAS  Google Scholar 

  10. C. Lothian, U. Lendahl, An evolutionarily conserved region in the second intron of the human nestin gene directs gene expression to CNS progenitor cells and to early neural crest cells. Eur. J. Neurosci. 9, 452–62 (1997)

    Article  PubMed  CAS  Google Scholar 

  11. P.J. Yaworsky, C. Kappen, Heterogeneity of neural progenitor cells revealed by enhancers in the nestin gene. Dev. Biol. 205, 309–21 (1999)

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. S. Tanaka, Y. Kamachi, A. Tanouchi, H. Hamada, N. Jing, H. Kondoh, Interplay of SOX and POU factors in regulation of the Nestin gene in neural primordial cells. Mol. Cell. Biol. 24(8834–46) (2004)

  13. D. Park, A.P. Xiang, F.F. Mao, L. Zhang, C.G. Di, X.M. Liu, Y. Shao, B.F. Ma, J.H. Lee, K.S. Ha, N. Walton, B.T. Lahn, Nestin is required for the proper self-renewal of neural stem cells. Stem Cells 28(2162–71) (2010)

  14. S. Wislet-Gendebien, F. Wautier, P. Leprince, B. Rogister, Plasticity of cultured mesenchymal stem cells: switch from nestin-positive to excitable neuron-like phenotype. Stem Cells 23, 392–402 (2005)

    Article  PubMed  CAS  Google Scholar 

  15. Y.J. Shin, H.L. Kim, J.M. Park, J.M. Cho, S.Y. Kim, M.Y. Lee, Characterization of nestin expression and vessel association in the ischemic core following focal cerebral ischemia in rats. Cell Tissue Res. 351, 383–95 (2013)

    Article  PubMed  CAS  Google Scholar 

  16. N. Sanai, A. Alvarez-Buylla, M.S. Berger, Neural stem cells and the origin of gliomas. N. Engl. J. Med. 353, 811–22 (2005)

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  18. O. Brustle, R.D. McKay, The neuroepithelial stem cell concept: implications for neuro-oncology. J Neurooncol. 24, 57–9 (1995)

    Article  PubMed  CAS  Google Scholar 

  19. S. Bao, Q. Wu, Z. Li, S. Sathornsumetee, H. Wang, R.E. McLendon, A.B... Hjelmeland, J.N. Rich, Targeting cancer stem cells through L1CAM suppresses glioma growth. Cancer Res. 68(6043–8) (2008)

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

    Article  PubMed  CAS  Google Scholar 

  21. P. Chinnaiyan, M. Wang, A.M. Rojiani, P.J. Tofilon, A. Chakravarti, K.K. Ang, H.Z. Zhang, E. Hammond, W. Jr Curran, M.P. Mehta, The prognostic value of nestin expression in newly diagnosed glioblastoma: report from the Radiation Therapy Oncology Group. Radiat. Oncol. 3, 32 (2008)

    Article  PubMed  PubMed Central  Google Scholar 

  22. R.H. Dahlrot, S.K. Hermansen, S. Hansen, B.W. Kristensen, What is the clinical value of cancer stem cell markers in gliomas? Int J Clin Exp Pathol. 6, 334–48 (2013)

    PubMed  CAS  PubMed Central  Google Scholar 

  23. M. Zhang, T. Song, L. Yang, R. Chen, L. Wu, Z. Yang, J. Fang, Nestin and CD133: valuable stem cell-specific markers for determining clinical outcome of glioma patients. J. Exp. Clin. Cancer Res. 27, 85 (2008)

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  24. F. Wan, C. Herold-Mende, B. Campos, F.S. Centner, C. Dictus, N. Becker, F. Devens, C. Mogler, J. Felsberg, N. Grabe, G. Reifenberger, P. Lichter, A. Unterberg, J.L. Bermejo, R. Ahmadi, Association of stem cell-related markers and survival in astrocytic gliomas. Biomarkers 16, 136–43 (2011)

    Article  PubMed  CAS  Google Scholar 

  25. G. Sica, G. Lama, C. Anile, M.C. Geloso, G.L.A. Torre, P. De Bonis, G. Maira, L. Lauriola, M. Jhanwar-Uniyal, A. Mangiola, Assessment of angiogenesis by CD105 and nestin expression in peritumor tissue of glioblastoma. Int. J. Oncol. 38, 41–9 (2011)

    PubMed  Google Scholar 

  26. T. Milde, T. Hielscher, H. Witt, M. Kool, S.C. Mack, H.E. Deubzer, I. Oehme, M. Lodrini, A. Benner, M.D. Taylor, A. von Deimling, A.E. Kulozik, S.M. Pfister, O. Witt, A. Korshunov, Nestin expression identifies ependymoma patients with poor outcome. Brain Pathol. 22(848–60) (2012)

  27. T. Strojnik, G.V. Røsland, P.O. Sakariassen, R. Kavalar, T. Lah, Neural stem cell markers, nestin and musashi proteins, in the progression of human glioma: correlation of nestin with prognosis of patient survival. Surg. Neurol. 68, 133–43 (2007)

    Article  PubMed  Google Scholar 

  28. N. Wagner, K.D. Wagner, H. Scholz, K.M. Kirschner, A. Schedl, Intermediate filament protein nestin is expressed in developing kidney and heart and might be regulated by the Wilms’ tumor suppressor Wt1. Am. J. Physiol. Regul. Integr. Comp. Physiol. 291, R779–87 (2006)

    Article  PubMed  CAS  Google Scholar 

  29. J. Chen, S. Boyle, M. Zhao, W. Su, K. Takahashi, L. Davis, M. Decaestecker, T. Takahashi, M.D. Breyer, C.M. Hao, Differential expression of the intermediate filament protein nestin during renal development and its localization in adult podocytes. J. Am. Soc. Nephrol. 17, 1283–91 (2006)

    Article  PubMed  CAS  Google Scholar 

  30. T. Sakairi, K. Hiromura, S. Yamashita, S. Takeuchi, M. Tomioka, H. Ideura, A. Maeshima, Y. Kaneko, T. Kuroiwa, M. Nangaku, T. Takeuchi, Y. Nojima, Nestin expression in the kidney with an obstructed ureter. Kidney Int. 72, 307–18 (2007)

    Article  PubMed  CAS  Google Scholar 

  31. W. Liu, Y. Zhang, S. Liu, Q. Liu, J. Hao, Y. Shi, S. Zhao, H. Duan, The expression of intermediate filament protein nestin and its association with cyclin-dependent kinase 5 in the glomeruli of rats with diabetic nephropathy. Am. J. Med. Sci. 345(470–7) (2013)

  32. B. Bussolati, S. Bruno, C. Grange, U. Ferrando, G. Camussi, Identification of a tumor-initiating stem cell population in human renal carcinomas. FASEB J. 22, 3696–705 (2008)

    Article  PubMed  CAS  Google Scholar 

  33. S. Gupta, C. Verfaillie, D. Chmielewski, S. Kren, K. Eidman, J. Connaire, Y. Heremans, T. Lund, M. Blackstad, Y. Jiang, A. Luttun, M.E. Rosenberg, Isolation and characterization of kidney-derived stem cells. J. Am. Soc. Nephrol. 17, 3028–40 (2006)

    Article  PubMed  CAS  Google Scholar 

  34. L. da Silva Meirelles, P.C. Chagastelles, N.B. Nardi, Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J. Cell Sci. 119, 2204–13 (2006)

    Article  PubMed  Google Scholar 

  35. M.D. Plotkin, M.S. Goligorsky, Mesenchymal cells from adult kidney support angiogenesis and differentiate into multiple interstitial cell types including erythropoietin-producing fibroblasts. Am J Physiol Renal Physiol. 291, F902–12 (2006)

    Article  PubMed  CAS  Google Scholar 

  36. E. Hunziker, M. Stein, Nestin-expressing cells in the pancreatic islets of Langerhans. Biochem. Biophys. Res. Commun. 271, 116–9 (2000)

    Article  PubMed  CAS  Google Scholar 

  37. H. Zulewski, E.J. Abraham, M.J. Gerlach, P.B. Daniel, W. Moritz, B. Müller, M. Vallejo, M.K. Thomas, J. Habener, Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes 50, 521–33 (2001)

    Article  PubMed  CAS  Google Scholar 

  38. T. Klein, Z. Ling, H. Heimberg, O.D. Madsen, R.S. Heller, P. Serup, Nestin is expressed in vascular endothelial cells in the adult human pancreas. J Histochem Cytochem 51, 697–706 (2003)

    Article  PubMed  CAS  Google Scholar 

  39. J. Lardon, I. Rooman, L. Bouwens, Nestin expression in pancreatic stellate cells and angiogenic endothelial cells. Histochem. Cell Biol. 117, 535–40 (2002)

    Article  PubMed  CAS  Google Scholar 

  40. H. Ueno, Y. Yamada, R. Watanabe, E. Mukai, M. Hosokawa, A. Takahashi, A. Hamasaki, H. Fujiwara, S. Toyokuni, M. Yamaguchi, J. Takeda, Y. Seino, Nestin-positive cells in adult pancreas express amylase and endocrine precursor Cells. Pancreas 31, 126–31 (2005)

    Article  PubMed  CAS  Google Scholar 

  41. L. Zhang, T.P. Hong, J. Hu, Y.N. Liu, Y.H. Wu, L.S. Li, Nestin-positive progenitor cells isolated from human fetal pancreas have phenotypic markers identical to mesenchymal stem cells. World J. Gastroenterol. 11(2906–11) (2005)

  42. H. Huang, X. Tang, Phenotypic determination and characterization of nestin-positive precursors derived from human fetal pancreas. Lab Invest. 83, 539–47 (2003)

    Article  PubMed  CAS  Google Scholar 

  43. R. Gao, J. Ustinov, M.A. Pulkkinen, K. Lundin, O. Korsgren, T. Otonkoski, Characterization of endocrine progenitor cells and critical factors for their differentiation in human adult pancreatic cell culture. Diabetes 52(2007–15) (2003)

  44. M.K. Treutelaar, J.M. Skidmore, C.L. Dias-Leme, M. Hara, L. Zhang, D. Simeone, D.M. Martin, C.F. Burant, Nestin-lineage cells contribute to the microvasculature but not endocrine cells of the islet. Diabetes 52(2503–12) (2003)

  45. R.K. Humphrey, N. Bucay, G.M. Beattie, A. Lopez, C.A. Messam, V. Cirulli, A. Hayek, Characterization and isolation of promoter-defined nestin-positive cells from the human fetal pancreas. Diabetes 52, 2519–25 (2003)

    Article  PubMed  CAS  Google Scholar 

  46. N. Bardeesy, R.A. DePinho, Pancreatic cancer biology and genetics. Nat. Rev. Cancer 2, 897–909 (2002)

    Article  PubMed  CAS  Google Scholar 

  47. C. Gilles, M. Polette, J.M. Zahm, J.M. Tournier, L. Volders, J.M. Foidart, P. Birembaut, Vimentin contributes to human mammary epithelial cell migration. J. Cell Sci. 112, 4615–25 (1999)

    PubMed  CAS  Google Scholar 

  48. Y. Matsuda, Z. Naito, K. Kawahara, N. Nakazawa, M. Korc, T. Ishiwata, Nestin is a novel target for suppressing pancreatic cancer cell migration, invasion and metastasis. Cancer Biol. Ther. 11, 512–23 (2011)

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  49. M. Kawamoto, T. Ishiwata, K. Cho, E. Uchida, M. Korc, Z. Naito, T. Tajiri, Nestin expression correlates with nerve and retroperitoneal tissue invasion in pancreatic cancer. Hum. Pathol. 40, 189–98 (2009)

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  50. N. Ikeda, M. Adachi, T. Taki, C. Huang, H. Hashida, A. Takabayashi, M. Sho, Y. Nakajima, H. Kanehiro, M. Hisanaga, H. Nakano, M. Miyake, Prognostic significance of angiogenesis in human pancreatic cancer. Br. J. Cancer 79, 1553–63 (1999)

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  51. K. Kuwahara, T. Sasaki, Y. Kuwada, M. Murakami, S. Yamasaki, K. Chayama, Expressions of angiogenic factors in pancreatic ductal carcinoma: a correlative study with clinicopathologic parameters and patient survival. Pancreas 26, 344–9 (2003)

    Article  PubMed  CAS  Google Scholar 

  52. K. Yamahatsu, Y. Matsuda, T. Ishiwata, E. Uchida, Z. Naito, Nestin as a novel therapeutic target for pancreatic cancer via tumor angiogenesis. Int. J. Oncol. 40, 1345–57 (2012)

    PubMed  CAS  Google Scholar 

  53. A.P. Meert, M. Paesmans, B. Martin, P. Delmotte, T. Berghmans, J.M. Verdebout, J.J. Lafitte, C. Mascaux, J.P. Sculier, The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis. Br. J. Cancer 87, 694–701 (2002)

    Article  PubMed  PubMed Central  Google Scholar 

  54. D. Yamazaki, S. Kurisu, T. Takenawa, Regulation of cancer cell motility through actin reorganization. Cancer Sci. 96, 379–86 (2005)

    Article  PubMed  CAS  Google Scholar 

  55. X. Liu, Y. Zhang, [Microtubule-associated protein 2 and nestin expressions in human embryonic and fetal gastric tissues]. Nan Fang Yi Ke Da Xue Xue Bao. 32, 1328–31 (2012)

    PubMed  CAS  Google Scholar 

  56. S. Dhingra, W. Feng, R.E. Brown, Z. Zhou, T. Khoury, R. Zhang, D. Tan, Clinicopathologic significance of putative stem cell markers, CD44 and nestin, in gastric adenocarcinoma. Int J Clin Exp Pathol. 4, 733–41 (2011)

    PubMed  CAS  PubMed Central  Google Scholar 

  57. T. Ishiwata, Y. Matsuda, Z. Naito, Nestin in gastrointestinal and other cancers: effects on cells and tumor angiogenesis. World J. Gastroenterol. 17, 409–18 (2011)

    Article  PubMed  PubMed Central  Google Scholar 

  58. C. Wiese, A. Rolletschek, G. Kania, A. Navarrete-Santos, S.V. Anisimov, B. Steinfarz, K.V. Tarasov, S.A. Brugh, I. Zahanich, C. Rüschenschmidt, H. Beck, P. Blyszczuk, J. Czyz, J.F. Heubach, U. Ravens, O. Horstmann, L. St-Onge, T. Braun, O. Brüstle, K.R. Boheler, A.M. Wobus, Signals from embryonic fibroblasts induce adult intestinal epithelial cells to form nestin-positive cells with proliferation and multilineage differentiation capacity in vitro. Stem Cells 24, 2085–97 (2006)

    Article  PubMed  CAS  Google Scholar 

  59. N. Teranishi, Z. Naito, T. Ishiwata, N. Tanaka, K. Furukawa, T. Seya, S. Shinji, T. Tajiri, Identification of neovasculature using nestin in colorectal cancer. Int. J. Oncol. 30, 593–603 (2007)

    PubMed  CAS  Google Scholar 

  60. S. Hirota, A. Ohashi, T. Nishida, K. Isozaki, K. Kinoshita, Y. Shinomura, Y. Kitamura, Gain-of-function mutations of platelet-derived growth factor receptor alpha gene in gastrointestinal stromal tumors. Gastroenterology 125, 660–7 (2003)

    Article  PubMed  CAS  Google Scholar 

  61. M. Sarlomo-Rikala, A.J. Kovatich, A. Barusevicius, M. Miettinen, CD117: a sensitive marker for gastrointestinal stromal tumors that is more specific than CD34. Mod. Pathol. 11, 728–34 (1998)

    PubMed  CAS  Google Scholar 

  62. M. van de Rijn, M.R. Hendrickson, R.V. Rouse, CD34 expression by gastrointestinal tract stromal tumors. Hum. Pathol. 25, 766–71 (1994)

    Article  PubMed  Google Scholar 

  63. M. Miettinen, J. Lasota, Gastrointestinal stromal tumors–definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch. 438, 1–12 (2001)

    Article  PubMed  CAS  Google Scholar 

  64. T. Tsujimura, C. Makiishi-Shimobayashi, J. Lundkvist, U. Lendahl, K. Nakasho, A. Sugihara, T. Iwasaki, M. Mano, N. Yamada, K. Yamashita, A. Toyosaka, N. Terada, Expression of the intermediate filament nestin in gastrointestinal stromal tumors and interstitial cells of Cajal. Am. J. Pathol. 158, 817–23 (2001)

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  65. J.M. Vanderwinden, K. Gillard, M.H. De Laet, C.A. Messam, S.N. Schiffmann, Distribution of the intermediate filament nestin in the muscularis propria of the human gastrointestinal tract. Cell Tissue Res. 309, 261–8 (2002)

    Article  PubMed  CAS  Google Scholar 

  66. J. Johnston, E.B. Helwig, Granular cell tumors of the gastrointestinal tract and perianal region: a study of 74 cases. Dig. Dis. Sci. 26, 807–16 (1981)

    Article  PubMed  CAS  Google Scholar 

  67. G.B. Rossi, M. de Bellis, P. Marone, A. De Chiara, S. Losito, A. Tempesta, Granular cell tumors of the colon: report of a case and review of the literature. J. Clin. Gastroenterol. 30, 197–9 (2000)

    Article  PubMed  CAS  Google Scholar 

  68. J.R. Parfitt, C.A. McLean, M.G. Joseph, C.J. Streutker, S. Al-Haddad, D.K. Driman, Granular cell tumours of the gastrointestinal tract: expression of nestin and clinicopathological evaluation of 11 patients. Histopathology 48, 424–30 (2006)

    Article  PubMed  CAS  Google Scholar 

  69. R. Pardal, M.F. Clarke, S.J. Morrison, Applying the principles of stem-cell biology to cancer. Nat. Rev. Cancer 3, 895–902 (2003)

    Article  PubMed  CAS  Google Scholar 

  70. J. Marx, Cancer research. Mutant stem cells may seed cancer. Science. 301, 1308–10 (2003)

    Article  PubMed  CAS  Google Scholar 

  71. T. Liu, F. Xu, X. Du, D. Lai, T. Liu, Y. Zhao, Q. Huang, L. Jiang, W. Huang, W. Cheng, Z. Liu, Establishment and characterization of multi-drug resistant, prostate carcinoma-initiating stem-like cells from human prostate cancer cell lines 22RV1. Mol. Cell. Biochem. 340, 265–73 (2010)

    Article  PubMed  CAS  Google Scholar 

  72. M.J. Pfeiffer, F.P. Smit, J.P. Sedelaar, J.A. Schalken, Steroidogenic enzymes and stem cell markers are upregulated during androgen deprivation in prostate cancer. Mol. Med. 17, 657–64 (2011)

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  73. P. Apostolou, M. Toloudi, M. Chatziioannou, E. Ioannou, I. Papasotiriou, Cancer stem cells stemness transcription factors expression correlates with breast cancer disease stage. Curr Stem Cell Res Ther. 7, 415–9 (2012)

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  75. C. Liu, X. Cao, Y. Zhang, H. Xu, R. Zhang, Y. Wu, P. Lu, F. Jin, Co-expression of Oct-4 and Nestin in human breast cancers. Mol. Biol. Rep. 39, 5875–81 (2012)

    Article  PubMed  CAS  Google Scholar 

  76. C. Liu, B. Chen, J. Zhu, R. Zhang, F. Yao, F. Jin, H. Xu, P. Lu, Clinical implications for nestin protein expression in breast cancer. Cancer Sci. 101, 815–9 (2010)

    Article  PubMed  CAS  Google Scholar 

  77. S. Parry, K. Savage, C. Marchiò, J.S. Reis-Filho, Nestin is expressed in basal-like and triple negative breast cancers. J. Clin. Pathol. 61, 1045–50 (2008)

    Article  PubMed  CAS  Google Scholar 

  78. H. Li, P. Cherukuri, N. Li, V. Cowling, M. Spinella, M. Cole, A.K. Godwin, W. Wells, J. DiRenzo, Nestin is expressed in the basal/myoepithelial layer of the mammary gland and is a selective marker of basal epithelial breast tumors. Cancer Res. 67, 501–10 (2007)

    Article  PubMed  CAS  Google Scholar 

  79. O. Rogelsperger, C. Ekmekcioglu, W. Jäger, M. Klimpfinger, R. Königsberg, D. Krenbek, F. Sellner, T. Thalhammer, Coexpression of the melatonin receptor 1 and nestin in human breast cancer specimens. J. Pineal Res. 46, 422–32 (2009)

    Article  PubMed  CAS  Google Scholar 

  80. D.X. Tan, L.C. Manchester, M.P. Terron, L.J. Flores, R.J. Reiter, One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species? J. Pineal Res. 42, 28–42 (2007)

    Article  PubMed  CAS  Google Scholar 

  81. F. Peyrot, C. Ducrocq, Potential role of tryptophan derivatives in stress responses characterized by the generation of reactive oxygen and nitrogen species. J. Pineal Res. 45, 235–46 (2008)

    Article  PubMed  CAS  Google Scholar 

  82. P.A. Witt-Enderby, N.M. Radio, J.S. Doctor, V.L. Davis, Therapeutic treatments potentially mediated by melatonin receptors: potential clinical uses in the prevention of osteoporosis, cancer and as an adjuvant therapy. J. Pineal Res. 41, 297–305 (2006)

    Article  PubMed  CAS  Google Scholar 

  83. V. Srinivasan, D.W. Spence, S.R. Pandi-Perumal, I. Trakht, D.P. Cardinali, Therapeutic actions of melatonin in cancer: possible mechanisms. Integr Cancer Ther. 7, 189–203 (2008)

    Article  PubMed  CAS  Google Scholar 

  84. A. Korkmaz, E.J. Sanchez-Barcelo, D.X. Tan, R.J. Reiter, Role of melatonin in the epigenetic regulation of breast cancer. Breast Cancer Res. Treat. 115, 13–27 (2009)

    Article  PubMed  CAS  Google Scholar 

  85. L. Lai, L. Yuan, Q. Chen, C. Dong, L. Mao, B. Rowan, T. Frasch, S.M. Hill, The Galphai and Galphaq proteins mediate the effects of melatonin on steroid/thyroid hormone receptor transcriptional activity and breast cancer cell proliferation. J. Pineal Res. 45, 476–88 (2008)

    Article  PubMed  CAS  Google Scholar 

  86. J.H. Lee, H.J. Park, Y.A. Kim, D.H. Lee, J.K. Noh, C.H. Kwon, S.M. Jung, S.K. Lee, The phenotypic characteristic of liver-derived stem cells from adult human deceased donor liver. Transplant. Proc. 44, 1110–2 (2012)

    Article  PubMed  CAS  Google Scholar 

  87. W.T. Bin, L.M. Ma, Q. Xu, X.L. Shi, Embryonic hepatocyte transplantation for hepatic cirrhosis: efficacy and mechanism of action. World J. Gastroenterol. 18(4), 309–22 (2012)

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  88. S. Reister, C. Kordes, I. Sawitza, D. Häussinger, The epigenetic regulation of stem cell factors in hepatic stellate cells. Stem Cells Dev. 20, 1687–99 (2011)

    Article  PubMed  CAS  Google Scholar 

  89. J.M. Luk, J. Burchard, C. Zhang, A.M. Liu, K.F. Wong, F.H. Shek, N.P. Lee, S.T. Fan, R.T. Poon, I. Ivanovska, U. Philippar, M.A. Cleary, C.A. Buser, P.M. Shaw, C.N. Lee, D.G. Tenen, H. Dai, M. Mao, DLK1-DIO3 genomic imprinted microRNA cluster at 14q32.2 defines a stemlike subtype of hepatocellular carcinoma associated with poor survival. J. Biol. Chem. 286, 30706–13 (2011)

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  90. X.R. Yang, Y. Xu, B. Yu, J. Zhou, S.J. Qiu, G.M. Shi, B.H. Zhang, W.Z. Wu, Y.H. Shi, B. Wu, G.H. Yang, Y. Ji, J. Fan, High expression levels of putative hepatic stem/progenitor cell biomarkers related to tumour angiogenesis and poor prognosis of hepatocellular carcinoma. Gut 59, 953–62 (2010)

    Article  PubMed  CAS  Google Scholar 

  91. M. Aihara, K. Sugawara, S. Torii, M. Hosaka, H. Kurihara, N. Saito, T. Takeuchi, Angiogenic endothelium-specific nestin expression is enhanced by the first intron of the nestin gene. Lab Invest. 84, 1581–92 (2004)

    Article  PubMed  CAS  Google Scholar 

  92. J. Mokry, D. Cízková, S. Filip, J. Ehrmann, J. Osterreicher, Z. Kolár, D. English, Nestin expression by newly formed human blood vessels. Stem Cells Dev. 13, 658–64 (2004)

    Article  PubMed  CAS  Google Scholar 

  93. S. Suzuki, J. Namiki, S. Shibata, Y. Mastuzaki, H. Okano, The neural stem/progenitor cell marker nestin is expressed in proliferative endothelial cells, but not in mature vasculature. J. Histochem. Cytochem. 58, 721–30 (2010)

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  94. K. Gravdal, O.J. Halvorsen, S.A. Haukaas, L.A. Akslen, Proliferation of immature tumor vessels is a novel marker of clinical progression in prostate cancer. Cancer Res. 69, 4708–15 (2009)

    Article  PubMed  CAS  Google Scholar 

  95. Y. Matsuda, M. Hagio, T. Ishiwata, Nestin: a novel angiogenesis marker and possible target for tumor angiogenesis. World J. Gastroenterol. 19, 42–8 (2013)

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  96. C. Calabrese, H. Poppleton, M. Kocak, T.L. Hogg, C. Fuller, B. Hamner, E.Y. Oh, M.W. Gaber, D. Finklestein, M. Allen, A. Frank, I.T. Bayazitov, S.S. Zakharenko, A. Gajjar, A. Davidoff, R.J. Gilbertson, A perivascular niche for brain tumor stem cells. Cancer Cell 11, 69–82 (2007)

    Article  PubMed  CAS  Google Scholar 

  97. D. Wen, L. Ni, L. You, L. Zhang, Y. Gu, C.M. Hao, J. Chen, Upregulation of nestin in proximal tubules may participate in cell migration during renal repair. Am J Physiol Renal Physiol. 303, F1534–44 (2012)

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. 2nd Department of Propedeutic Surgery, Athens University Medical School, Laiko General Hospital, 17 Agiou Thoma Street, 11527, Athens, Greece

    Ekaterini Christina Tampaki, Konstantinos Kontzoglou & Gregory Kouraklis

  2. Department of General and Visceral Surgery, University Clinic of Heidelberg, 69120, Heidelberg, Germany

    Athanasios Tampakis

  3. Department of Surgery, University hospital of Basel, Spitalstraße 21, 4056, Basel, Switzerland

    Athanasios Tampakis & Walter P. Weber

  4. University of Heidelberg, School of Medicine, Heidelberg, Germany

    Ekaterini Christina Tampaki

  5. 1st Department of Pathology, School of Medicine, National University of Athens, Athens, Greece

    Lydia Nakopoulou

Authors
  1. Ekaterini Christina Tampaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lydia Nakopoulou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Athanasios Tampakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Konstantinos Kontzoglou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Walter P. Weber
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gregory Kouraklis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Athanasios Tampakis.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tampaki, E.C., Nakopoulou, L., Tampakis, A. et al. Nestin involvement in tissue injury and cancer - a potential tumor marker?. Cell Oncol. 37, 305–315 (2014). https://doi.org/10.1007/s13402-014-0193-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13402-014-0193-5

Keywords

Search

Navigation