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The influence of the microenvironment on liver-specific tumor cell colonization in a murine tumor model

  • Original Papers
  • Experimental Oncology
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Summary

Malignant tumors often show an organ-specific metastatic spread. Some cells of the primary apparently bear an affinity for growing in the microenvironment of certain organs. After i.v. injection of myofibrosarcoma cells from the primary ER 15-P into the tail vein of male C57/BI6J mice, metastases developed in various organs. A tumor cell line (ER 15-Me3) isolated from liver metastases of the primary was found to colonize preferentially to the liver. To find out whether the liver specificity of the tumor cell line ER 15-Me3 depended on the hepatic microenvironment, tumor cells from this line were transplanted i.m. into the thighs of mice once (ER 15-Me3 i.m.1) or 5 times (ER 15-Me3 i.m.5), and then injected into the tail vein of mice. A part of the 5-times passaged tumor cell line was also injected into the mesenteric vein (ER 15-Me3 i.m.5-Me1) prior to reinjection into the tail vein. Results: After i.v. administration of tumor cells from the first i.m. passage of the tumor cell line (ER 15-Me3 i.m.1) into the tail vein, the liver-specific metastatic behavior of tumor cells remained stable. Following the i.v. injection of tumor cells from the 5th i.m. transplant generation of the tumor cell line (ER 15-Me3 i.m.5) into the tail vein, organ distribution was similar to that of the primary. After only 1 mesenteric vein passage of the 5-times i.m. transplanted line ER 15-Me3 i.m.5-Me1 followed by i.v. injection into the tail vein, did tumor cells regain their liver-specific colonizing potential. Thus, the liver-specific tumor cell line seems to contain a small number of other tumor cell populations from the unselected primary. In the muscle, these tumor cells have a growth advantage over the liver-specific cells, while the latter will grow better in the liver. This indicates that the microenvironment may be one important factor influencing the organ-specific metastatic pattern of tumor cells.

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References

  • Auerbach R, Wei CL, Pardon E, Gumkowski F, Kaminska G, Kaminski M (1987) Specificity of adhesion between murine tumor cells and capillary endothelium: an in vitro correlate of preferential metastasis in vivo. Cancer Res 47:1492–1496

    Google Scholar 

  • Bresalier RS, Hujanen ES, Raper SE, Roll FJ, Itzkowitz SH, Martin GF, Kim YS (1987) An animal model for colon cancer metastasis: establishment and characterization of murine cell lines with enhanced liver metastasizing ability. Cancer Res 47:1398–1406

    Google Scholar 

  • Brunson KW, Nicolson GL (1980) Experimental brain metastases. In: Weiss L, Gilbert HA, Posner JB (eds) Brain metastasis. Martinus Nijhoff, The Hague-Boston-London, pp 50–65

    Google Scholar 

  • Chan WS, Jackson A, Turner GA (1984) Differences in surface expression of WGA-binding proteins of cells from a lymphosarcoma and its liver metastases. Br J Cancer 49:181–191

    Google Scholar 

  • Cheingsong-Popov R, Robinson P, Altevogt P, Schirrmacher V (1983) A mouse hepatocyte carbohydrate-specific receptor and its interaction with liver-metastasizing tumor cells. Int J Cancer 32:359–366

    Google Scholar 

  • Cook GMW, Seaman GVF, Weiss L (1963) Physicochemical differences between ascitic and solid forms of sarcoma 37 cells. Cancer Res 23:1813–1818

    Google Scholar 

  • Diamandopoulos GT (1979) Microenvironmental influences on the in vivo behavior of neoplastic lymphocytes. Proc Natl Acad Sci USA 76:6456–6460

    Google Scholar 

  • Edel G (1984) Tierexperimentelle Untersuchungen zur Organpräferenz von metastasierenden Tumoren. Verh Dtsch Ges Pathol 68:206–210

    Google Scholar 

  • Edel G (1988) Mechanism of liver-specific metastatic tumor spread in a murine tumor model. J Cancer Res Clin Oncol 114:47–58

    Google Scholar 

  • Edel G, Grundmann E (1984) Selection of liver-colonizing tumor cells from a murine fibrosarcoma induced by methylcholanthrene. J Cancer Res Clin Oncol 108:274–280

    Google Scholar 

  • Ewing J (1928) Neoplastic disease, a treatise on tumors, 3rd edn. Saunders, Philadelphia, pp 77–89

    Google Scholar 

  • Fidler IJ (1970) Metastasis: quantitative analysis of distribution and fate of tumor emboli labeled with 125J-5-iodo-2′-desoxyuridine. J Natl Cancer Inst 45:775–782

    Google Scholar 

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

    Google Scholar 

  • Fidler IJ, Gersten DM, Riggs CW (1977) Relationship of host immune status to tumor cell arrest, distribution, and survival in experimental metastasis. Cancer 40:46–55

    Google Scholar 

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

    Google Scholar 

  • Harlos JP, Weiss L (1983) Differences in the peripheries of Lewis lung tumor cells growing in different sites in the mouse. Int J Cancer 32:745–750

    Google Scholar 

  • Hart IR (1982) “Seed and soil” revisited: mechanisms of site specific metastasis. Cancer Metastasis Rev 1:5–17

    Google Scholar 

  • Hart IR, Fidler IJ (1980) Role of organ selectivity in the determination of metastatic patterns of B 16 melanoma. Cancer Res 40:2281–2287

    Google Scholar 

  • Horak E, Darling DL, Tarin D (1986) Analysis of organ-specific effects on metastatic tumor formation by studies in vitro. J Natl Cancer Inst 76:913–922

    Google Scholar 

  • Hujanen ES, Terranova VP (1985) Migration of tumor cells to organ-derived chemoattractants. Cancer Res 45:3517–3521

    Google Scholar 

  • Juacaba SF, Jones LD, Tarin D (1983) Organ preferences in metastatic colony formation by spontaneous mammary carcinoma after intraarterial inoculation. Invasion Metastasis, 3:208–220

    Google Scholar 

  • Kieda C, Monsigny M (1986) Involvement of membrane sugar receptors and membrane glycoconjugates in the adhesion of 3LL cell subpopulations to cultured pulmonary cells. Invasion Metastasis 6:347–366

    Google Scholar 

  • Kieran MW, Longenecker BM (1983) Organ specific metastasis with special reference to avian systems. Cancer Metastasis Rev 2:165–182

    Google Scholar 

  • McGuire EJ, Mascali JJ, Grady SR, Nicolson GL (1984) Involvement of cell-cell adhesion molecules in liver colonizing by metastatic murine lymphoma/lymphosarcoma variants. Clin Exp Metastasis 2:213–222

    Google Scholar 

  • Meromsky L, Lotan R, Raz A (1986) Implications of endogenous tumor cell surface lectins as mediators of cellular interactions and lung colonization. Cancer Res 46:5270–5275

    Google Scholar 

  • Middelkoop OP, Bavel P van, Calafat J, Roos E, (1985) Hepatocyte surface molecule involved in the adhesion of TA3 mammary carcinoma cells to rat hepatocyte cultures. Cancer Res 45:3825–3835

    Google Scholar 

  • Naito S, Eschenbach AC v., Giavazzi R, Fidler IJ (1986) Growth and metastasis of tumor cells isolated from a human renal cell carcinoma implanted into different organs of nude mice. Cancer Res 46:4109–4115

    Google Scholar 

  • Naito S, Giavazzi R, Fidler IJ (1987) Correlation between the in vitro interaction of tumor cells with an organ environment and metastatic behavior in vitro. Invasion Metastasis 7:16–29

    Google Scholar 

  • Netland PA, Zetter BR (1985) Metastatic potential of B 16 melanoma cells after in vitro selection for organ-specific adherence. J Cell Biol 101:720–724

    Google Scholar 

  • Nicolson GL (1982) Cancer metastasis. Organ colonization and the cell surface properties of malignant cells. Biochim Biophys Acta 695:113–176

    Google Scholar 

  • Nicolson GL (1987a) Differential growth properties of metastatic large cell lymphoma in target organ-conditioned medium. Exp Cell Res 168:572–577

    Google Scholar 

  • Nicolson GL (1987b) Tumor cell instability, diversification, and progression to the metastatic phenotype: from oncogene to oncofetal expression. Cancer Res 47:1473–1487

    Google Scholar 

  • Nicolson GL, Custead SE (1982) Tumor metastasis is not due to adaptation of cells to a new organ environment. Science 215:176–178

    Google Scholar 

  • Nicolson GL, Dulski KM (1986) Organ specificity of metastatic tumor colonization is related to organ-selective growth properties of malignant cells. Int J Cancer 38:289–294

    Google Scholar 

  • Nicolson GL, Dulski KM, Basson C, Welch DR (1985) Preferential organ attachment and invasion in vitro by B 16 melanoma cells selected for differing metastatic colonization and invasive properties. Invasion Metastasis 5:144–158

    Google Scholar 

  • Paget S (1889) The distribution of secondary growth in cancer of the breast. Lancet I:571–573

    Google Scholar 

  • Poste G, Fidler IJ (1980) The pathogenesis of cancer metastasis. Nature 283:139–145

    Google Scholar 

  • Potter KM, Juacaba SF, Price JE, Tarin D (1983) Observations on organ distribution of fluorescein-labelled tumour cells released intravascularly. Invasion Metastasis 3:221–233

    Google Scholar 

  • Price JE, Carr D, Tarin D (1984) Spontaneous and induced metastasis of naturally occurring tumors in mice: analysis of cell shedding into the blood. J Natl Cancer Inst 73:1319–1326

    Google Scholar 

  • Price JE, Ankerman SL, Fidler IJ (1986) Evidence that the process of murine melanoma metastasis is sequential and selective and contains stochastic elements. Cancer Res 46:5172–5178

    Google Scholar 

  • Roos E (1984) Cellular adhesion, invasion and metastasis Biochim Biophys Acta 738:263–284

    Google Scholar 

  • Ryd W, Hagmar B, Erkell LJ (1986) Characterization of two murine tumor sublines selected purely in vivo for specific metastatic patterns. Invasion Metastasis 6:21–32

    Google Scholar 

  • Schirrmacher V (1985) Cancer metastasis: experimental approaches, theoretical concepts, and impacts for treatment strategies. Adv Cancer Res 43:1–73

    Google Scholar 

  • Schirmacher V, Altevogt P, Fogel M, Dennis J, Waller CA, Barz D, Schwartz R, Cheingsong-Popov R, Springer G, Robinson PJ, Nebe T, Brossmer W, Vlodaysky I, Pawletz PJ, Zimmermann HP, Uhlenbruck G (1982) Importance of cell surface carbohydrates in cancer cell adhesion, invasion, and metastasis. Does sialic acid direct metastatic behavior?. Invasion Metastasis 2:313–360

    Google Scholar 

  • Sugarbaker EV (1981) Patterns of metastases in human malignancies. Cancer Biol Rev 2:235–278

    Google Scholar 

  • Sugarbaker EV, Weingrad DN, Roseman JM (1982) Observations on cancer metastasis in man. In: Liotta LA, Hart JR (eds) Invasion and metastasis. Martinus Nijhoff. The Hague-Boston-London, p 427–465

    Google Scholar 

  • Talmadge JE, Fidler IJ (1982) Cancer metastasis is selective or random depending on the parent tumor population. Nature 297:593–594

    Google Scholar 

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

    Google Scholar 

  • Uhlenbruck G, Beuth HJ, Oette R, Schotten T, Ko HL, Roszkowski R, Roszkowski W, Lütticken R, Pulverer G (1986) Lektine und die Organotropie der Metastasierung. Dtsch Med Wochenschr 111:991–995

    Google Scholar 

  • Vollmers HP, Birchmeier W (1983) Monoclonal antibodies inhibit the adhesion of mouse B16 melanoma cells in vitro and block lung metastasis in vivo. Proc Natl Acad Sci USA 80:3729–3733

    Google Scholar 

  • Weiss L (1985) Principles of metastasis. Academic Press, Orlando London

    Google Scholar 

  • Weiss L, Harlos JP (1979) Differences in the peripheries of Walker cancer cells growing in different sites in the rat. Cancer Res 39:2481–2485

    Google Scholar 

  • Weiss L, Bronk J, Pickren JW, Lane WW (1981) Metastatic patterns and target organ arterial blood flow. Invasion Metastasis 1:126–135

    Google Scholar 

  • Weiss L, Voit A, Lane WW (1984a) Metastatic pattern in patients with carcinomas of the lower esophagus and upper rectum. Invasion Metastasis 4:47–60

    Google Scholar 

  • Weiss L, Ward PM, Harlos JP, Holmes C (1984b) Target organ pattern of tumors in mice following the arterial dissemination of B 16 melanoma cells. Int J Cancer 33:825–830

    Google Scholar 

  • Weiss L, Grundmann E, Torhorst J, Hartveit F, Moberg I, Eder M, Fenoglio-Preiser CM, Napier J, Horne CHW, Lopez MJ, Shaw-Dunn RI, Sugar J, Davies JD, Day DW, Harlos JP (1986a) Haematogenous metastatic patterns in colonic carcinoma: an analysis of 1541 necropsies. J Pathol 150:195–203

    Google Scholar 

  • Weiss L, Ward PM, Harlos JP (1986b) The stability of kidney-induced selection of Lewis lung tumor cell populations, and their metastasis-related behavior. Int J Cancer 38:207–213

    Google Scholar 

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  1. Gerhard-Domagk-Institut für Pathologie, University of Münster, Domagkstrasse 17, D-4400, Münster, Federal Republic of Germany

    G. Edel

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Edel, G. The influence of the microenvironment on liver-specific tumor cell colonization in a murine tumor model. J Cancer Res Clin Oncol 114, 163–169 (1988). https://doi.org/10.1007/BF00417831

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  • DOI: https://doi.org/10.1007/BF00417831

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