Skip to main content

Advertisement

SpringerLink
Log in

Lung Cancer with Gastrointestinal Metastasis - Review of Theories of Metastasis with Three Rare Case Descriptions

  • Review Paper
  • Published:
Cancer Microenvironment

Abstract

Approximately 1 in 14 men and women during their lifetime will be diagnosed with lung cancer, which is the leading cause of cancer-related mortality in the world. As of January 1, 2008, there were about 373,500 men and women living with lung cancer in the United States. Fewer than 60,000 of these are estimated to be alive by January 2013, reflecting a poor overall 5-year relative survival rate of under 16 %. With metastatic cancer, the overall 5-year survival is meager 4 %. On the other hand, the overall five-year survival is over 50 % when the cancer is still in the localized stage. However, unfortunately, more than half of cases of lung cancer are diagnosed at an advanced stage Howlader et al. (2010). Cancer metastasis, the single most critical prognostic factor, is still poorly understood and a highly complex phenomenon. The most common sites of lung cancer metastasis are the lymph nodes, liver, adrenals, brain and bones. The gastrointestinal (GI) tract is an exceptionally rare site of metastasis; with only a handful of cases reported in the literature Centeno et al. (Lung Cancer, 18: 101–105, 1997); Hirasaki et al. (World J Gastroenterol, 14: 5481–5483, 2008); Carr and Boulos (Br J Surg, 83: 647, 1996); Otera et al. (Eur Respir Rev, 19: 248–252, 2010); Antler et al. (Cancer, 49: 170–172, 1982); Fujiwara et al. (Gen Thorac Cardiovasc Surg, 59: 748–752, 2011); Stinchcombe et al. (J Clin Oncol, 24: 4939–4940, 2006); John et al. (J Postgrad Med, 48: 199–200, 2002); Carroll and Rajesh (Eur J Cardiothorac Surg, 19: 719–720, 2001); Brown et al. (Dis Colon Rectum, 23: 343–345, 1980). We report three cases of non-small cell (squamous cell) lung cancer with GI tract metastasis—two in the colon and one in the jejunum. Then we present a review of literature exploring various theories of metastasis, as an attempt to understand the reason of preferential tumor metastasis.

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. Howlader NNA, Krapcho M, Neyman N, Aminou R, Waldron W, et al. (2010) SEER cancer statistics review, 1975–2008, National cancer institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2008/, based on November 2010 SEER data submission

  2. Centeno Cortes C, Borau Clavero MJ, Sanz Rubiales A et al (1997) Intestinal bleeding in disseminated non-small cell lung cancer. Lung Cancer 18:101–105

    Article  PubMed  CAS  Google Scholar 

  3. Hirasaki S, Suzuki S, Umemura S et al (2008) Asymptomatic colonic metastases from primary squamous cell carcinoma of the lung with a positive fecal occult blood test. World J Gastroenterol 14:5481–5483

    Article  PubMed  Google Scholar 

  4. Carr CS, Boulos PB (1996) Two cases of solitary metastases from carcinoma of the lung presenting as primary colonic tumours. Br J Surg 83:647

    Article  PubMed  CAS  Google Scholar 

  5. Otera H, Ikeda F, Nakagawa S et al (2010) Intussusception of small intestine due to metastasis of large cell carcinoma of the lung with a rhabdoid phenotype. Eur Respir Rev 19:248–252

    Article  PubMed  CAS  Google Scholar 

  6. Antler AS, Ough Y, Pitchumoni CS et al (1982) Gastrointestinal metastases from malignant tumors of the lung. Cancer 49:170–172

    Article  PubMed  CAS  Google Scholar 

  7. Fujiwara A, Okami J, Tokunaga T et al (2011) Surgical treatment for gastrointestinal metastasis of non-small-cell lung cancer after pulmonary resection. Gen Thorac Cardiovasc Surg 59:748–752

    Article  PubMed  Google Scholar 

  8. Stinchcombe TE, Socinski MA, Gangarosa LM et al (2006) Lung cancer presenting with a solitary colon metastasis detected on positron emission tomography scan. J Clin Oncol 24:4939–4940

    Article  PubMed  Google Scholar 

  9. John AK, Kotru A, Pearson HJ (2002) Colonic metastasis from bronchogenic carcinoma presenting as pancolitis. J Postgrad Med 48:199–200

    PubMed  CAS  Google Scholar 

  10. Carroll D, Rajesh PB (2001) Colonic metastases from primary squamous cell carcinoma of the lung. Eur J Cardiothorac Surg 19:719–720

    Article  PubMed  CAS  Google Scholar 

  11. Brown KL, Beg RA, Demany MA et al (1980) Rare metastasis of primary bronchogenic carcinoma to sigmoid colon: report of a case. Dis Colon Rectum 23:343–345

    Article  PubMed  CAS  Google Scholar 

  12. Pezzuto A, Mariotta S, Fioretti F et al (2013) Metastasis to the colon from lung cancer presenting with severe hyponatremia and dyspnea in a young male: a case report and review of the literature. Oncology Letters 5:1477–1480

    PubMed  Google Scholar 

  13. Stenbygaard LE, Sorensen JB, Olsen JE (1997) Metastatic pattern at autopsy in non-resectable adenocarcinoma of the lung–a study from a cohort of 259 consecutive patients treated with chemotherapy. Acta Oncol 36:301–306

    Article  PubMed  CAS  Google Scholar 

  14. Lardinois D, Weder W, Roudas M et al (2005) Etiology of solitary extrapulmonary positron emission tomography and computed tomography findings in patients with lung cancer. J Clin Oncol 23:6846–6853

    Article  PubMed  Google Scholar 

  15. Paget S (1989) The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev 8:98–101

    PubMed  CAS  Google Scholar 

  16. Ewing J (1922) Neoplastic diseases—a treatise on tumors. Second Edition. Aufl: Philadelphi and London W. B. Saunders Company

  17. Nowell PC (1976) The clonal evolution of tumor cell populations. Science 194:23–28

    Article  PubMed  CAS  Google Scholar 

  18. Fidler IJ, Kripke ML (1977) Metastasis results from preexisting variant cells within a malignant tumor. Science 197:893–895

    Article  PubMed  CAS  Google Scholar 

  19. Shoushtari AN, Szmulewitz RZ, Rinker-Schaeffer CW (2011) Metastasis-suppressor genes in clinical practice: lost in translation? Nat Rev Clin Oncol 8:333–342

    PubMed  CAS  Google Scholar 

  20. Yoshida BA, Sokoloff MM, Welch DR et al (2000) Metastasis-suppressor genes: a review and perspective on an emerging field. J Natl Cancer Inst 92:1717–1730

    Article  PubMed  CAS  Google Scholar 

  21. Goldberg SF, Harms JF, Quon K et al (1999) Metastasis-suppressed C8161 melanoma cells arrest in lung but fail to proliferate. Clin Exp Metastasis 17:601–607

    Article  PubMed  CAS  Google Scholar 

  22. Hsieh SM, Look MP, Sieuwerts AM et al (2009) Distinct inherited metastasis susceptibility exists for different breast cancer subtypes: a prognosis study. Breast Cancer Res 11:R75

    Article  PubMed  Google Scholar 

  23. Hunter KW, Alsarraj J (2009) Gene expression profiles and breast cancer metastasis: a genetic perspective. Clin Exp Metastasis 26:497–503

    Article  PubMed  CAS  Google Scholar 

  24. Hurst DR, Welch DR (2011) Unraveling the enigmatic complexities of BRMS1-mediated metastasis suppression. FEBS Lett 585:3185–3190

    Article  PubMed  CAS  Google Scholar 

  25. Ma Q, Jiang Q, Pu Q et al (2013) MicroRNA-143 inhibits migration and invasion of human non-small-cell lung cancer and its relative mechanism. Int J Biol Sci 9:680–692

    Article  PubMed  Google Scholar 

  26. Chandrasoma PTC (1998) The lung: III. Neoplasms. In: Chandrasoma PTC (ed) Hrsg. Concise Pathology 3rd. Aufl. McGraw-Hill, New York

    Google Scholar 

  27. Cameron MD, Schmidt EE, Kerkvliet N et al (2000) Temporal progression of metastasis in lung: cell survival, dormancy, and location dependence of metastatic inefficiency. Cancer Res 60:2541–2546

    PubMed  CAS  Google Scholar 

  28. Yoshida K, Fujikawa T, Tanabe A et al (1993) Quantitative analysis of distribution and fate of human lung cancer emboli labeled with 125I-5-iodo-2′-deoxyuridine in nude mice. Surg Today 23:979–983

    Article  PubMed  CAS  Google Scholar 

  29. Groom AC, MacDonald IC, Schmidt EE et al (1999) Tumour metastasis to the liver, and the roles of proteinases and adhesion molecules: new concepts from in vivo videomicroscopy. Can J Gastroenterol 13:733–743

    PubMed  CAS  Google Scholar 

  30. Murphy P, Alexander P, Senior PV et al (1988) Mechanisms of organ selective tumour growth by bloodborne cancer cells. Br J Cancer 57:19–31

    Article  PubMed  CAS  Google Scholar 

  31. Thiery JP, Acloque H, Huang RY et al (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139:871–890

    Article  PubMed  CAS  Google Scholar 

  32. Pawelek JM, Chakraborty AK (2008) The cancer cell–leukocyte fusion theory of metastasis. Adv Cancer Res 101:397–444

    Article  PubMed  CAS  Google Scholar 

  33. Swartz MA, Kristensen CA, Melder RJ et al (1999) Cells shed from tumours show reduced clonogenicity, resistance to apoptosis, and in vivo tumorigenicity. Br J Cancer 81:756–759

    Article  PubMed  CAS  Google Scholar 

  34. Ting CC, Rodrigues D, Ting RC et al (1979) Suppression of T cell-mediated immunity by tumor cells: immunogenicity versus immunosuppression and preliminary characterization of the suppressive factors. Int J Cancer 24:644–655

    Article  PubMed  CAS  Google Scholar 

  35. Hoon DS, Irie RF, Cochran AJ (1988) Gangliosides from human melanoma immunomodulate response of T cells to interleukin-2. Cell Immunol 111:410–419

    Article  PubMed  CAS  Google Scholar 

  36. Mareel MM, Behrens J, Birchmeier W et al (1991) Down-regulation of E-cadherin expression in Madin Darby canine kidney (MDCK) cells inside tumors of nude mice. Int J Cancer 47:922–928

    Article  PubMed  CAS  Google Scholar 

  37. Moreno-Bueno G, Cubillo E, Sarrio D et al (2006) Genetic profiling of epithelial cells expressing E-cadherin repressors reveals a distinct role for Snail, Slug, and E47 factors in epithelial-mesenchymal transition. Cancer Res 66:9543–9556

    Article  PubMed  CAS  Google Scholar 

  38. Fang QX, Lu LZ, Yang B et al (2010) L1, beta-catenin, and E-cadherin expression in patients with colorectal cancer: correlation with clinicopathologic features and its prognostic significance. J Surg Oncol 102:433–442

    Article  PubMed  Google Scholar 

  39. McClelland MR, Carskadon SL, Zhao L et al (2007) Diversity of the angiogenic phenotype in non-small cell lung cancer. Am J Respir Cell Mol Biol 36:343–350

    Article  PubMed  CAS  Google Scholar 

  40. Bremnes RM, Camps C, Sirera R (2006) Angiogenesis in non-small cell lung cancer: the prognostic impact of neoangiogenesis and the cytokines VEGF and bFGF in tumours and blood. Lung Cancer 51:143–158

    Article  PubMed  Google Scholar 

  41. Fontanini G, Bigini D, Vignati S et al (1995) Microvessel count predicts metastatic disease and survival in non-small cell lung cancer. J Pathol 177:57–63

    Article  PubMed  CAS  Google Scholar 

  42. Joyce JA, Pollard JW (2009) Microenvironmental regulation of metastasis. Nat Rev Cancer 9:239–252

    Article  PubMed  CAS  Google Scholar 

  43. Zigler M, Kamiya T, Brantley EC et al (2011) PAR-1 and thrombin: the ties that bind the microenvironment to melanoma metastasis. Cancer Res 71:6561–6566

    Article  PubMed  CAS  Google Scholar 

  44. Villares GJ, Zigler M, Wang H et al (2008) Targeting melanoma growth and metastasis with systemic delivery of liposome-incorporated protease-activated receptor-1 small interfering RNA. Cancer Res 68:9078–9086

    Article  PubMed  CAS  Google Scholar 

  45. Nierodzik ML, Karpatkin S (2006) Thrombin induces tumor growth, metastasis, and angiogenesis: evidence for a thrombin-regulated dormant tumor phenotype. Cancer cell 10:355–362

    Article  PubMed  CAS  Google Scholar 

  46. Arora P, Ricks TK, Trejo J (2007) Protease-activated receptor signalling, endocytic sorting and dysregulation in cancer. J Cell Sci 120:921–928

    Article  PubMed  CAS  Google Scholar 

  47. Yang E, Boire A, Agarwal A et al (2009) Blockade of PAR1 signaling with cell-penetrating pepducins inhibits Akt survival pathways in breast cancer cells and suppresses tumor survival and metastasis. Cancer Res 69:6223–6231

    Article  PubMed  CAS  Google Scholar 

  48. Darmoul D, Gratio V, Devaud H et al (2003) Aberrant expression and activation of the thrombin receptor protease-activated receptor-1 induces cell proliferation and motility in human colon cancer cells. Am J Pathol 162:1503–1513

    Article  PubMed  CAS  Google Scholar 

  49. Chay CH, Cooper CR, Gendernalik JD et al (2002) A functional thrombin receptor (PAR1) is expressed on bone-derived prostate cancer cell lines. Urology 60:760–765

    Article  PubMed  Google Scholar 

  50. Wilson SR, Gallagher S, Warpeha K et al (2004) Amplification of MMP-2 and MMP-9 production by prostate cancer cell lines via activation of protease-activated receptors. The Prostate 60:168–174

    Article  PubMed  CAS  Google Scholar 

  51. Gay LJ, Felding-Habermann B (2011) Contribution of platelets to tumour metastasis. Nat Rev Cancer 11:123–134

    Article  PubMed  CAS  Google Scholar 

  52. Bambace NM, Holmes CE (2011) The platelet contribution to cancer progression. J Thromb Haemost 9:237–249

    Article  PubMed  CAS  Google Scholar 

  53. Pilatova K, Greplova K, Demlova R et al (2013) Role of platelet chemokines, PF-4 and CTAP-III, in cancer biology. J Hematol Oncol 6:42

    Article  PubMed  CAS  Google Scholar 

  54. Palumbo JS, Talmage KE, Massari JV et al (2005) Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells. Blood 105:178–185

    Article  PubMed  CAS  Google Scholar 

  55. Ballas ZK, Buchta CM, Rosean TR et al (2013) Role of NK cell subsets in organ-specific murine melanoma metastasis. PLoS One 8:e65599

    Article  PubMed  CAS  Google Scholar 

  56. Ballas ZK, Krieg AM, Warren T et al (2001) Divergent therapeutic and immunologic effects of oligodeoxynucleotides with distinct CpG motifs. J Immunol 167:4878–4886

    PubMed  CAS  Google Scholar 

  57. Borczuk AC, Toonkel RL, Powell CA (2009) Genomics of lung cancer. Proc Am Thorac Soc 6:152–158

    Article  PubMed  CAS  Google Scholar 

  58. Larsen JE, Pavey SJ, Bowman R et al (2007) Gene expression of lung squamous cell carcinoma reflects mode of lymph node involvement. Eur Respir J 30:21–25

    Article  PubMed  CAS  Google Scholar 

  59. Vachani A, Nebozhyn M, Singhal S et al (2007) A 10-gene classifier for distinguishing head and neck squamous cell carcinoma and lung squamous cell carcinoma. Clin Cancer Res 13:2905–2915

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of Interest

None

Author information

Authors and Affiliations

  1. University of Pittsburgh Medical Center, Pittsburgh, USA

    Rohtesh S. Mehta & Vida A. Passero

  2. VA Pittsburgh Healthcare System, Pittsburgh, USA

    Andrew D. Liman, Vida A. Passero & Agnes K. Liman

  3. Division of Hematology-Oncology, UPMC Cancer Pavilion, Room 463, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA

    Rohtesh S. Mehta

Authors
  1. Rohtesh S. Mehta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrew D. Liman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vida A. Passero
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Agnes K. Liman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rohtesh S. Mehta.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mehta, R.S., Liman, A.D., Passero, V.A. et al. Lung Cancer with Gastrointestinal Metastasis - Review of Theories of Metastasis with Three Rare Case Descriptions. Cancer Microenvironment 6, 203–211 (2013). https://doi.org/10.1007/s12307-013-0135-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12307-013-0135-1

Keywords

Search

Navigation