Skip to main content
SpringerLink
Log in

Paracrine growth regulation of human colon carcinoma organ-specific metastasis

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Summary

The process of cancer metastasis consists of a series of steps resulting in the spread of malignant cells beyond the site of origin and formation of metastases in distant organs. The outcome of this nonrandom process depends, in part, on the interaction of unique tumor cells with a compatible organ microenvironment. The molecular basis of the intrinsic capacity of distinct malignant cells to colonize specific organs and the degree to which host factors influence this process is under intense investigation. Biological analyses of human colon carcinoma tumors obtained from surgical specimens and implanted orthotopically into athymic nude mice revealed that these tumors are heterogeneous for metastatic properties. Moreover, recent evidence using this model suggest that whereas nonmetastatic and highly metastatic cells can grow at local sites, growth in the secondary liver-specific site was associated only with highly metastatic HCC cells. These cells also respond to mitogenic signals produced by damaged normal tissues, suggesting that physiological signals can be utilized by neoplastic cells. Molecular characterization of highly metastatic HCC cells selected in the nude mouse model as well asin situ mRNA hybridization of archival HCC surgical specimens for specific growth factor receptors correlated with the malignant cell's ability to respond to organ-specific growth factors. This article will focus on biological and molecular evidence supporting the hypothesis that organ-derived, paracrine growth factors regulate the site-specific growth of receptive malignant cells that possess the appropriate receptors.

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

Similar content being viewed by others

References

  1. Fidler IJ, Kripke ML: Metastasis results from pre-existing variant cells within a malignant tumor. Science 197: 893–895, 1977

    Google Scholar 

  2. Fidler IJ: Special Lecture: critical factors in the biology of human cancer metastasis: twenty-eight G.H.A. Clowes Memorial Lecture. Cancer Res 50: 6130–6138, 1990

    Google Scholar 

  3. Hart IR: ‘Seed and Soil’ revisited: mechanisms of site specific metastasis. Cancer Metastasis Rev 1: 5–17, 1982

    Google Scholar 

  4. Nicolson GL: Cancer Metastasis: tumor cell and host organ properties important in metastasis to specific secondary sites. Biochim Biophys Acta 948: 175–224, 1988

    Google Scholar 

  5. Fidler IJ, Radinsky R: Editorial: genetic control of cancer metastasis. J Natl Cancer Inst 82: 166–168, 1990

    Google Scholar 

  6. Nicolson GL: Cancer progression and growth: relationship of paracrine and autocrine growth mechanisms to organ preference of metastasis. Expt Cell Res 204: 171–180, 1993

    Google Scholar 

  7. Fidler IJ, Balch CM: The biology of cancer metastasis and implications for therapy. Curr Probl Surg 24: 137–209, 1987

    Google Scholar 

  8. Kerbel RS: Growth dominance of metastatic cancer cell: cellular and molecular aspects. Adv Cancer Res 55: 87–132, 1990

    Google Scholar 

  9. Nowell PC: The clonal evolution of tumor cell populations. Science 194: 23–28, 1976

    Google Scholar 

  10. Staroselsky AN, Radinsky R, Fidler IJ, Pathak S, Chernajovsky Y, Frost P: The use of molecular genetic markers to demonstrate the effect of organ environment on clonal dominance in human renal cell carcinoma grown in nude mice. Int J Cancer 51: 130–138, 1992

    Google Scholar 

  11. Radinsky R: Growth factors and their receptors in metastasis. Semin Cancer Biol 2: 169–177, 1991

    Google Scholar 

  12. Paget S: The distribution of secondary growths in cancer of the breast. Lancet 1: 571–573, 1889

    Google Scholar 

  13. Tarin D, Price JE, Kettlewell MGW, Souter RG, Vass ACR, Crossley B: Mechanisms of human tumor metastasis studied in patients with peritoneovenous shunts. Cancer Res 44: 3584–3592, 1984

    Google Scholar 

  14. Ewing J: Neoplastic diseases. WB Saunders, Philadelphia, 1928

    Google Scholar 

  15. Sugarbaker EV: Patterns of metastasis in human malignancies. Cancer Biol Rev 2: 235–278, 1981

    Google Scholar 

  16. Giavazzi R, Campbell DE, Jessup JM, Cleary K, Fidler IJ: Metastatic behavior of tumor cells isolated from primary and metastatic human colorectal carcinomas implanted into different sites of nude mice. Cancer Res 46: 1928–1933, 1986

    Google Scholar 

  17. Fidler IJ: Orthotopic implantation of human colon carcinomas into nude mice provides a valuable model for the biology and therapy of metastasis. Cancer Metastasis Rev 10: 229–243, 1991

    Google Scholar 

  18. Liotta LA: Tumor invasion and metastasis - role of the extracellular matrix: Rhoads Memorial Award Lecture. Cancer Res 46: 1–7, 1986

    Google Scholar 

  19. Jessup JM, Gallick GE: The biology of colorectal carcinoma. Curr Probl Cancer 16: 263–328, 1992

    Google Scholar 

  20. Giavazzi R, Jessup JM, Campbell DE, Walker SM, Fidler IJ: Experimental nude mouse model of human colorectal cancer liver metastasis. J Natl Cancer Inst 77: 1303–1308, 1986

    Google Scholar 

  21. Morikawa K, Walker SM, Jessup JM, Fidler IJ:In vivo selection of highly metastatic cells from surgical specimens of different colon carcinomas implanted into nude mice. Cancer Res 48: 1943–1948, 1988

    Google Scholar 

  22. Morikawa K, Walker SM, Nakajima M, Pathak S, Jessup JM, Fidler IJ: Influence of organ environment on the growth, selection, and metastasis of human colon carcinoma cells in nude mice. Cancer Res 48: 6863–6871, 1988

    Google Scholar 

  23. Cornil T, Man MS, Fernandez B, Kerbel RS: Enhanced tumorigenicity, melanogenesis and metastasis of a human malignant melanoma observed after subdermal implantation in nude mice. J Natl Cancer Inst 81: 938–944, 1989

    Google Scholar 

  24. Shafie SM, Liotta LA: Formation of metastasis by human breast carcinoma cells (MCF-7) in nude mice. Cancer Lett 11: 81–87, 1980

    Google Scholar 

  25. Stephenson RA, Dinney CPN, Gohji K, Ordonez NG, Killion JJ, Fidler IJ: Metastatic model for human prostate cancer using orthotopic implantation in nude mice. J Natl Cancer Inst 84: 951–957, 1992

    Google Scholar 

  26. McLemore TL, Liu MC, Blacker PC, Gregg M, Alley MC, Abbott BJ, Shoemaker RH, Bohlman ME, Litterst CC, Hubbard WC, Brennan RH, McMahon JB, Fine DL, Eggleston JC, Mayo JG, Boyd MR: Novel intrapulmonary model for orthotopic propagation of human lung cancers in athymic nude mice. Cancer Res 47: 5132–5140, 1987

    Google Scholar 

  27. Radinsky R, Culp LA: Clonal dominance of select subsets of viral Kirstenras +-transformed 3T3 cells during tumor progression. Int J Cancer 48: 148–159, 1991

    Google Scholar 

  28. Kerbel RS: Commentary: expression of multi-cytokine resistance and multi-growth factor independence in advanced stage metastatic cancer: malignant melanoma as a paradigm. Am J Pathol 141: 519–524, 1992

    Google Scholar 

  29. August DA, Ottow RT, Sugarbaker EV: Clinical perspectives of human colorectal cancer metastasis. Cancer Metastasis Rev 3: 303–325, 1984

    Google Scholar 

  30. Price JE, Daniels LM, Campbell DE, Giavazzi R: Organ distribution of experimental metastases of a human colorectal carcinoma injected in nude mice. Clin Expt Metastasis 7: 55–68, 1989

    Google Scholar 

  31. Sidransky D, Mikkelsen T, Schwechheimer K, Rosenblum ML, Cavanee W, Vogelstein B: Clonal expansion of p53 mutant cells is associated with brain tumor progression. Nature (London) 355: 846–847, 1992

    Google Scholar 

  32. Radinsky R, Kraemer PM, Proffitt MR, Culp LA: Clonal diversity of the Kirsten-ras oncogene during tumor progression in athymic nude mice: mechanisms of amplification and rearrangement. Cancer Res 48: 4941–4953, 1988

    Google Scholar 

  33. Radinsky R, Weisberg HZ, Staroselsky AN, Fidler IJ: Expression level of thenm23 gene in clonal populations of metastatic murine and human neoplasms. Cancer Res (Adv in Brief) 52: 5808–5814, 1992

    Google Scholar 

  34. Friedman E: A primary culture system of human colon carcinoma cells and its use in evaluating differentiation therapy. In: Augenlicht L (ed) Cell and Molecular Biology of Colon Cancer. CRC Press, Boca Raton, 1989, pp 69–85

    Google Scholar 

  35. Malden L, Novak U, Burgess A: Expression of transforming growth factor alpha messenger RNA in the normal and neoplastic gastro-intestinal tract. Int J Cancer 43: 380–384, 1989

    Google Scholar 

  36. Markowitz SD, Molkentin K, Gerbic C, Jackson J, Stellato T, Willson JKV: Growth stimulation by coexpression of transforming growth-factor-α and epidermal growth factor-receptor in normal and adenomatous human colon epithelium. J Clin Invest 86: 356–362, 1990

    Google Scholar 

  37. Deuel TF: Polypeptide growth factors: roles in normal and abnormal cell growth. Annu Rev Cell Biol 3: 443–492, 1987

    Google Scholar 

  38. Burgess AW: Epidermal growth factor and transforming growth factor α. Br Med Bull 45: 401–424, 1989

    Google Scholar 

  39. Goodlad R, Wilson T, Lenton W, Gregory H, McCullagh K, Wright N: Intravenous but not intragastric urogastrone-EGF is trophic to the intestine of parenterally fed rats. Gut 28: 573–582, 1987

    Google Scholar 

  40. Bradley S, Garfinkle G, Walker E, Salem R, Chen L, Steele G: Increased expression of the epidermal growth factor receptor on human colon carcinoma cells. Arch Surg 121: 1242–1247, 1986

    Google Scholar 

  41. Coffey R, Goustin A, Soderquiat A, Shipley G, Wolfshohl J, Carpenter G, Moses H: Transforming growth factor α and β expression in human colon cancer lines: implication for an autocrine model. Cancer Res 47: 4590–4594, 1987

    Google Scholar 

  42. Watkins L, Brattain M, Levin A: Modulation of a high molecular weight form of transforming growth factor-α in human colon carcinoma cell lines. Cancer Lett 40: 59–70, 1988

    Google Scholar 

  43. Bates S, Valverius E, Ennis B, Bronzert D, Sheridan J, Stampfer M, Mendelsohn J, Lippman M, Dickson R: Expression of the transforming growth factor-α/epidermal growth factor receptor pathway in normal human breast epithelial cells. Endocrinology 126: 596–607, 1990

    Google Scholar 

  44. Gherardi E, Stoker M: Hepatocyte growth factor-scatter factor: mitogen, motogen, and met. Cancer Cells 3: 227–232, 1991

    Google Scholar 

  45. LaBrecque DR: Editorial: hepatocyte growth factor - how do I know thee? Let me count the ways. Gastroenterology 103: 1686–1691, 1992

    Google Scholar 

  46. Wolf HK, Zarnegar R, Michalopoulous GK: Localization of hepatocyte growth factor in human and rat tissues: an immunohistochemical study. Hepatology 14: 488–494, 1991

    Google Scholar 

  47. Rubin JS, Osada H, Finch PW, Taylor WG, Rudikoff F, Aaronson SA: Purification and characterization of a newly identified growth factor specific for epithelial cells. Proc Natl Acad Sci USA 86: 802–806, 1989

    Google Scholar 

  48. Rubin JS, Chan AM-L, Bottaro DP, Burgess WH, Taylor WG, Cech AC, Hirschfield DW, Wong J, Miki T, Finch PW, Aaronson SA: A broad-spectrum human lung fibroblast-derived mitogen is a variant of hepatocyte growth factor. Proc Natl Acad Sci USA 88: 415–419, 1991

    Google Scholar 

  49. Stocker M, Perryman M: An epithelial scatter factor released by embryo fibroblasts. J Cell Sci 77: 209–223, 1985

    Google Scholar 

  50. Weidner KM, Arakaki N, Hartman G, Vandekerckhove J, Weingart S, Rieder H, Fonatsch C, Tsubovchi H, Hishida T, Daikuhara Y, Birchmeier W: Evidence for the identity of human scatter factor and human hepatocyte growth factor. Proc Natl Acad Sci USA 88: 7001–7005, 1991

    Google Scholar 

  51. Weidner KM, Behrens J, Vandekerckhove J, Birchmeier W: Scatter factor: molecular characteristics and effect on the invasiveness of epithelial cells. J Cell Biol 111: 2097–2108, 1990

    Google Scholar 

  52. Jones FS, Rous P: On the cause of the localization of secondary tumours at point of injury. J Exp Med 20: 404–412, 1914

    Google Scholar 

  53. Agostino DE, Clifton EE: Trauma as a cause of location of blood borne metastases. Ann Surg 161: 97–102, 1965

    Google Scholar 

  54. Alexander JW, Altemeier WA: Susceptibility of injured tissues to hematogenous metastases: an experimental study. Ann Surg 159: 933–944, 1964

    Google Scholar 

  55. Murphy P, Alexander P, Kirklam N, Fleming J, Taylor L: Pattern of spread of bloodborne tumour. Br J Surg 73: 829–834, 1986

    Google Scholar 

  56. Orr FW, Adamson IYR, Young L: Promotion of pulmonary metastases in mice by bleomycin-induced endothelial injury. Cancer Res 46: 891–897, 1986

    Google Scholar 

  57. Robinson KP, Hoppe E: The development of bloodborne metastases: effect of local trauma and ischaemia. Arch Surg 85: 720–724, 1962

    Google Scholar 

  58. Skipper D, Jeffrey MJ, Cooper AJ, Alexander P, Taylor I: Enhanced growth of tumour cells in healing colonic anastomoses and laparotomy wounds. Int J Colorectal Disease 4: 172–177, 1989

    Google Scholar 

  59. Fisher ER, Fisher B: Experimental study of factors influencing development of hepatic metastases from circulating tumour cells. ACTA Cyto 9: 146–158, 1965

    Google Scholar 

  60. Loizidou MC, Lawrance RJ, Holt S, Carty NJ, Cooper AJ, Alexander P, Taylor I: Facilitation by partial hepatectomy of tumor growth within the rat liver following intraportal injection of syngeneic tumor cells. Clin Exp Met 9: 335–349, 1991

    Google Scholar 

  61. van Dale P, Galand P: Effect of partial hepatectomy on experimental liver invasion by intraportally injected colon carcinoma cells in rats. Invasion Met 8: 217–227, 1988

    Google Scholar 

  62. Michalopoulous GK: Liver regeneration: molecular mechanisms of growth control. FASEB J 4: 176–187, 1990

    Google Scholar 

  63. Fausto N, Mead J, Braun L, Thompson NL, Panzica M, Goyette M, Bell GI, Shank PR: Proto-oncogene expression and growth factors during liver regeneration. In: Becker FF, Slaga TF (eds) Critical Molecular Determinants of Carcinogenesis. University of Texas Press, Austin, 1987, pp 69–86

    Google Scholar 

  64. Mead JE, Fausto N: Transforming growth factor α may be a physiological regulator of liver regeneration by means of an autocrine mechanism. Proc Natl Acad Sci USA 86: 1558–1562, 1989

    Google Scholar 

  65. Grupposo PA, Mead JE, Fausto N: Transforming growth factor receptors in liver regeneration following partial hepatectomy in the rat. Cancer Res 50: 1464–1469, 1990

    Google Scholar 

  66. Noji S, Tashiro K, Koyama E, Nohno T, Ohyama K, Taniguchi S, Nakamura T: Expression of hepatocyte growth factor gene in endothelial and Kupffer cells of damaged rat livers, as revealed byin situ hybridization. Biochem Biophys Res Commun 173: 42–47, 1990

    Google Scholar 

  67. Bottaro DP, Robin JS, Falletto DL, Chan AML, Kmiecik TE, Vande Woude GF, Aaronson SA: Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science 251: 802–804, 1991

    Google Scholar 

  68. Naldini L, Vigna E, Narshimhan RP, Gaudino G, Zarnegar R, Michalopoulous GK, Comoglio PM: Hepatocyte growth factor (HGF) stimulates the tyrosine kinase activity of the receptor encoded by the proto-oncogene c-met. Oncogene 6: 501–504, 1991

    Google Scholar 

  69. Ullrich A, Schlessinger J: Signal transduction by receptors with tyrosine kinase activity. Cell 61: 203–212, 1990

    Google Scholar 

  70. Radinsky R, Flickinger KS, Kosir MA, Zardi L, Culp LA: Adhesion of Kirsten-ras+ tumor-progressing and Kirsten-ras− revertant 3t3 cells on fibronectin proteolytic fragments. Cancer Res 50: 4388–4400, 1990

    Google Scholar 

  71. Culp LA, Radinsky R, Lin W-C: Extracellular matrix interactions with tumor progressing cells: tumor versus cell typespecific mechanisms. In: Pretlow TG, Pretlow TP (eds) Biochemical and Molecular Aspects of Selected Cancers. Academic Press, Inc., Orlando, FL, Vol. 1, 1991, pp 99–149

    Google Scholar 

  72. Bradley SJ, Garfinkle G, Walker E, Salem R, Chen LB, Steele G: Increased expression of the epidermal growth receptor on human colon carcinoma cells. Arch Surg 121: 1242–1247, 1986

    Google Scholar 

  73. Herlyn M, Kath R, Williams N, Valyi-Nagy I, Rodeck U: Growth regulatory factors for normal, premalignant, and malignant human cellsin vitro. Adv Cancer Res 54: 213–234, 1990

    Google Scholar 

  74. Yarden Y, Ullrich A: Growth factor receptor tyrosine kinases. Annu Rev Biochem 57: 443–478, 1988

    Google Scholar 

  75. Giordano S, Zhen Z, Medico E, Gaudino G, Galimi F, Comoglio PM: Transfer of motogenic and invasive response to scatter factor/hepatocyte growth factor by transfection of human MET protooncogene. Proc Natl Acad Sci USA 90: 649–653, 1993

    Google Scholar 

  76. Shiota G, Rhoads DB, Wang TC, Nakamura T, Schmidt EV: Hepatocyte growth factor inhibits growth of hepatocellular carcinoma cells. Proc Natl Acad Sci USA 89: 373–377, 1992

    Google Scholar 

  77. Hamada J, Cavanaugh PG, Lotan O, Nicolson GL: Separable growth and migration factors for large-cell lymphoma cells secreted by microvascular endothelial cells derived from target organs for metastasis. Br J Cancer 66: 349–354, 1992

    Google Scholar 

  78. Okumura Y, Hamada J-I, Cavanaugh PG, Nicolson GL: Preferential growth stimulation of metastatic rat mammary adenocarcinoma cells by organ-derived syngeneic fibroblastsin vitro. Invasion Met 12: 275–283, 1993

    Google Scholar 

  79. Chung LWK: Fibroblasts are critical determinants in prostatic cancer growth and dissemination. Cancer Met Rev 10: 263–274, 1991

    Google Scholar 

  80. Yasui W, Sumiyoshi H, Hata J, Kameda T, Ochiai A, Ito H, Tahara E: Expression of epidermal growth factor receptor in human gastric and colonic carcinomas. Cancer Res 48: 137–141, 1988

    Google Scholar 

  81. Sainsbury JRC, Needham GK, Farndon JR, Malcom AJ, Harris AL: Epidermal-growth-factor receptor status as a predictor of early recurrence and death from breast cancer. Lancet 1: 1398–1402, 1987

    Google Scholar 

  82. Radinsky R, Bucana CD, Ellis LM, Sanchez R, Cleary KR, Brigati DJ, Fidler IJ: A rapid colorimetricin situ messenger RNA hybridization technique for analysis of epidermal growth factor receptor in paraffin-embedded surgical specimens of human colon carcinomas. Cancer Res (Adv in Brief) 53: 937–943, 1993

    Google Scholar 

  83. Bucana CD, Radinsky R, Dong Z, Sanchez R, Brigati DJ, Fidler IJ: A rapid colorimetricin situ mRNA hybridization technique using hyperbiotinylated oligonucleotide probes for analysis of mdr1 in mouse colon carcinoma cells. J Histochem Cytochem 41: 499–506, 1993

    Google Scholar 

  84. Park CS, Manahan LJ, Brigati D: Automated molecular pathology: one hourin situ DNA hybridization. J Histochem 14: 219–229, 1991

    Google Scholar 

  85. Iezzoni JC, Kang J-H, Montone KT, Reed JA, Brigati DJ: Colorimetric detection of herpes simplex virus by DNAin situ sandwich hybridization: a rapid, formamide-free, random oligomer-enhanced method. Nucleic Acids Res 20: 1149–1150, 1992

    Google Scholar 

  86. Ullrich A, Coussens L, Hayflick JS, Dull TJ, Gray A, Tam AW, Lee J, Yarden Y, Liberman TA, Schlessinger J, Downward J, Mayes ELV, Whittle N, Waterfield MD, Seeburg PH: Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. Nature (London) 309: 418–428, 1984

    Google Scholar 

  87. Finkelstein Y, Wolff M, Biegon A: Brain acetylcholinesterase after acute parathion poisoning: a comparative quantitative histochemical analysis post-mortem. Annu Neurol 24: 252–257, 1988

    Google Scholar 

  88. Lin W-C, Pretlow TP, Pretlow TG, Culp LA: High resolution analyses of two different classes of tumor cellsin situ tagged with alternative histochemical marker genes. Am J Pathol 141: 1331–1342, 1992

    Google Scholar 

  89. Lin W-C, Culp LA: Altered establishment clearance mechanisms during experimental micrometastasis with live and/or disabled bacteriallaz-tagged tumor cells. Invasion Met 12: 197–209, 1992

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cell Biology, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 173, 77030, Houston, Texas, USA

    Robert Radinsky

Authors
  1. Robert Radinsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Radinsky, R. Paracrine growth regulation of human colon carcinoma organ-specific metastasis. Cancer Metast Rev 12, 345–361 (1993). https://doi.org/10.1007/BF00665962

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00665962

Key words

Search

Navigation