Skip to main content
SpringerLink
Log in

Differential organ tissue adhesion, invasion, and growth properties of metastatic rat mammary adenocarcinoma cells

  • Report
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Metastatic lines and clones of the rat 13762NF mammary adenocarcinoma have been established that show reproducible spontaneous metastasis from the mammary fat pad to regional lymph node and lung. Poorly (MTC) and highly (MTLn3) metastatic cloned lines derived from tumor growing in the mammary fat pad (MTC) and its spontaneous lung metastasis (MTLn3) were testedin vitro for their abilities to attach to and invade into syngeneic organ tissue and to survive and grow in medium conditioned by target and nontarget syngeneic organ tissues. The highly metastatic MTLn3 cells adhered to and invaded target lung tissue at significantly higher rates than the MTC cells, and bound to and invaded other organ tissues although at lower rates than lung tissue. Similarly, the MTLn3 cells showed significantly higher growth stimulation by lung-conditioned medium than medium conditioned by other tissues. Poorly metastatic MTC cells were not significantly stimulated by any of the organ-conditioned media. The results are consistent with previous proposals that explain preferential organ metastasis in terms of ‘seed and soil’, and further suggest that metastasis of mammary tumors to specific organ secondary sites is mediated by specific properties, such as those involved in tumor-cell organ-cell adhesion, invasion, and growth.

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

References

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

    Google Scholar 

  2. Ewing J: A Treatise on Tumors, 3rd Ed. W.B. Saunders, Philadelphia, 1928

    Google Scholar 

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

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

    PubMed  Google Scholar 

  5. Nicolson GL: Organ specificity of tumor metastasis: Role of preferential adhesion, invasion, and growth of malignant cells at specific secondary sites. Cancer Metastasis Rev, 7: 143–188, 1988

    PubMed  Google Scholar 

  6. Poste G: Experimental systems for analysis of the malignant phenotype. Cancer Metastasis Rev 1: 141–199, 1982

    PubMed  Google Scholar 

  7. Hart IR: Seed and soil revisited. Mechanisms of site specific metastasis. Cancer Metastasis Rev 1: 5–16, 1982

    PubMed  Google Scholar 

  8. Tarin D, Price JE: Metastatic colonization potential of primary tumour cells in mice. Br J Cancer 39: 740–754, 1979

    PubMed  Google Scholar 

  9. Tarin D, Price JE: Influence of microenvironment and vascular anatomy on ‘metastatic’ colonization potential of mammary tumors. Cancer Res 41: 3604–3609, 1981

    PubMed  Google Scholar 

  10. Lichtner RB, Nicolson GL: Organization of cytoskeletal structures in 13762NF rat mammary adenocarcinoma cell lines and clones of varying metastatic potentials. Invasion Metastasis 7: 73–82, 1987

    PubMed  Google Scholar 

  11. Lichtner RB, Moskwa PS, Nicolson GL: Heterogeneous expression of cytokeratins in metastatic rat mammary adenocarcinoma cellsin vitro andin vivo. Invasion Metastasis 7: 367–383, 1987

    PubMed  Google Scholar 

  12. Neri A, Ruoslahti E, Nicolson GL: Distribution of fibronectin on clonal cell lines of a rat mammary adenocarcinoma growingin vitro andin vivo at primary and metastatic sites. Cancer Res 41: 5082–5095, 1981

    PubMed  Google Scholar 

  13. Neri A, Nicolson GL: Phenotypic drift of metastatic and cell surface properties of mammary adenocarcinoma cell clones during growthin vitro. Int J Cancer 28: 731–738, 1981

    PubMed  Google Scholar 

  14. Steck PA, Nicolson GL: Cell surface glycoproteins of 13762NF mammary adenocarcinoma clones of differing metastatic potentials. Exp Cell Res 147: 255–267, 1983

    PubMed  Google Scholar 

  15. Steck PA, North SM, Nicolson GL: Purification and partial characterization of a tumour metastasis-associated high Mr glycoprotein from rat 13762NF mammary adenocarcinoma cells. Biochem J 242: 779–787, 1987

    PubMed  Google Scholar 

  16. North SM, Nicolson GL: Effect of host immune status on the spontaneous metastasis of cloned cell lines of the 13762NF rat mammary adenocarcinoma. Br J Cancer 52: 747–755, 1985

    PubMed  Google Scholar 

  17. North SM, Steck PA, Nicolson GL: Monoclonal antibodies against cell surface antigens of the metastatic rat 13762NF mammary adenocarcinoma and their cross-reactivity with human breast carcinoma. Cancer Res 46: 6393–6399, 1986

    PubMed  Google Scholar 

  18. Neri A, Welch D, Kawaguchi T, Nicolson GL: Development and biologic properties of malignant cell sublines and clones of a spontaneously metastasizing rat mammary adenocarcinoma. J Natl Cancer Inst 68: 507–517, 1982

    PubMed  Google Scholar 

  19. Nicolson GL, Dulski K, Basson C, Welch DR: Preferential organ attachment and invasionin vitro by B16 melanoma cells selected for differing metastatic colonization and invasive properties. Invasion Metastasis 5: 144–158, 1985

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  21. Nicolson GL: Differential growth properties of metastatic large cell lymphoma cells in target organ-conditioned medium. Exp Cell Res 168: 572–577, 1987

    PubMed  Google Scholar 

  22. Updyke TV, Nicolson GL: Malignant melanoma cell lines selectedin vitro for increased homotypic adhesion properties have increased experimental metastatic potential. Clin Expl Metastasis 4: 273–284, 1986

    Google Scholar 

  23. Nicolson GL, Winkelhake JL: Organ specificity of blood-borne tumor metastasis determined by cell adhesion? Nature (London) 255: 230–232, 1975

    Google Scholar 

  24. North SM, Nicolson GL: Heterogeneity in the sensitivities of 13762NF mammary adenocarcinoma cell clones to cytolysis mediated by extra- and intratumoral macrophages. Cancer Res 45: 1453–1458, 1985

    PubMed  Google Scholar 

  25. Miner KM, Klostergaard J, Granger GA, Nicolson GL: Differences in the cytotoxic effects of activated peritoneal macrophages and J774 monocytic cells on metastatic variants of B16 melanoma. J Natl Cancer Inst 70: 717–724, 1983

    PubMed  Google Scholar 

  26. Miner KM, Nicolson GL: Differences in the sensitivities of murine metastatic lymphoma/lymphosarcoma variants to macrophage-mediated cytolysis and/or cytostasis. Cancer Res 43: 2063–2067, 1983

    PubMed  Google Scholar 

  27. Yamashina K, Fulton A, Heppner G: Differential sensitivity of metastatic versus nonmetastatic mammary tumor cells of macrophage-mediated cytostasis. J Natl Cancer Inst 75: 765–770, 1985

    PubMed  Google Scholar 

  28. Gasic GJ, Gasic TB, Galanti N, Johnson T, Murphy S: Platelet-tumor interactions in mice. The role of platelets in the spread of malignant disease. Int J Cancer 11: 704–718, 1973

    PubMed  Google Scholar 

  29. Estrada J, Nicolson GL: Tumor-cell-platelet aggregation does not correlate with metastatic potential of rat 13762NF mammary adenocarcinoma tumor cell clones. Int J Cancer 34: 101–110, 1984

    PubMed  Google Scholar 

  30. Nicolson GL: Metastatic tumor cell attachment and invasion assay utilizing vascular endothelial cell monolayers. J Histochem Cytochem 30: 214–220, 1982

    PubMed  Google Scholar 

  31. Price JE, Aukerman SL, FIdler IJ: Evidence that the process of murine melanoma metastasis is sequential and selective and contains stochastic elements. Cancer Res 46: 5172–5178, 1986

    PubMed  Google Scholar 

  32. Weiss L: Random and nonrandom processes in metastasis, and metastatic efficiency. Invasion Metastasis 3: 193–208, 1983

    PubMed  Google Scholar 

  33. Heuson JC, Paridaens R, Leclercq G: Endocrine concepts in relation to diagnosis and treatment of breast cancer. In: Rich MA, Hager JC, Furmanski P (eds): Understanding Breast Cancer. Marcel Dekker, New York, 1983, pp. 43–51

    Google Scholar 

  34. Lippman ME, Kickson RB, Kasid A, Gelmann E, Davidson N, McManaway M, Huff K, Bronzert D, Bates S, Swain S, Knabbe C: Autocrine and paracrine growth regulation of human breast cancer. J Steroid Biochem 24: 147–154, 1986

    PubMed  Google Scholar 

  35. Miller FR, Medina D, Heppner GH: Preferential growth of mammary tumors in intact mammary fat pads. Cancer Res 41: 3863–3867, 1981

    PubMed  Google Scholar 

  36. Miller FR, McInerney D: Epithelial component of hosttumor interactions in the orthotopic site preference of a mouse mammary tumor. Cancer Res, 48: 3698–3701, 1988

    PubMed  Google Scholar 

  37. Segaloff A: Hormones and breast cancer. Recent Prog Horm Res 22: 351–379, 1966

    PubMed  Google Scholar 

  38. Dabbous MK, Woolley DE, Haney L, Carter LM, Nicolson GL: Host-mediated effectors of tumor invasion: Role of mast cells in matrix degradation. Clin Expl Metastasis 4: 141–152, 1986

    Google Scholar 

  39. Dabbous MK, Walker R, Haney L, Carter LM, Nicolson GL, Wooley DE: Mast cells and matrix degradation at sites of tumour invasion in rat mammary adenocarcinoma. Br J Cancer 54: 459–465, 1986

    PubMed  Google Scholar 

  40. Nakajima M, Welch DR, Belloni PN, Nicolson GL: Degradation of basement membrane type IV collagen and lung subendothelial matrix by rat mammary adenocarcinoma cell clones of differing metastatic potentials. Cancer Res 47: 4869–4876, 1987

    PubMed  Google Scholar 

  41. Foulds L: The histologic analysis of mammary tumors of mice. II. The histology of responsiveness and progression. The origin of tumors. J Natl Cancer Inst 17: 713–754, 1956

    Google Scholar 

  42. Venter DJ, Kumar S, Tuzi NL, Gullick WJ: Overexpression of the c-erbB-2 oncoprotein in human breast carcinomas: Immunohistological assessment correlates with gene amplification. Lancet 1: 69–71, 1987

    PubMed  Google Scholar 

  43. van de Vijver M, van de Bersselaan R, Devilee P, Cornelisse C, Peterse J, Nusse R: Amplification of the neu (c-erbB-2) oncogene in human mammary tumors is relatively frequent and is often accompanied by amplification of the linked c-erbA oncogene. Mol Cell Biol 7: 2019–2023, 1987

    PubMed  Google Scholar 

  44. Kraus MH, Popescu NC, Amsbaugh SC, King CR: Overexpression of the EGF receptor-related proto-oncogeneerbB-2 in human mammary tumor cell lines by different molecular mechanisms. EMBO J 6: 605–610, 1987

    PubMed  Google Scholar 

  45. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235: 177–182, 1987

    PubMed  Google Scholar 

  46. Yamamoto T, Ikawa S, Akiyama T, Semba K, Nomura N, Miyajima N, Saito T, Toyoshima K: Similarity of the protein encoded by the human c-erbB-2 gene to epidermal growth factor receptor. Nature (London) 319: 230–234, 1986

    Google Scholar 

  47. Lichtner RB, Gallick GE, Nicolson GL: Pyrimido-pyrimidine modulation of EGF growth-promoting activity and p21ras expression in rat mammary adenocarcinoma cells. J Cell Physiol, in press, 1988

  48. Rodeck U, Herlyn M, Menssen HD, Furlanetto RW, Koprowski H: Metastatic but not primary melanoma cell lines growin vitro independently of exogenous growth factors. Int J Cancer 40: 687–690, 1987

    PubMed  Google Scholar 

  49. Liotta LA, Mandler R, Murano G, Katz DA, Gordon RK, Chang PK, Sciffman E: Autocrine motility factor. Proc Natl Acad Sci USA 83: 3302–3306, 1986

    PubMed  Google Scholar 

  50. Atnip KD, Carter LM, Nicolson GL, Dabbous MK: Chemotactic response of rat mammary adenocarcinoma cell clones to tumor-derived cytokines. Biochem Biophys Res Commun 146: 996–1002, 1987

    PubMed  Google Scholar 

  51. Hujanen ES, Terranova VP: Migration of tumor cells to organ-derived chemoattractants. Cancer Res 74: 829–838, 1985

    Google Scholar 

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

    PubMed  Google Scholar 

  53. Szanuiawska B, Majewski S, Maninski MJ, Noremberg K, Swierz M, Janik P: Stimulatory and inhibitory activities of lung-conditioned medium on the growth of normal and neoplastic cellsin vitro. J Natl Cancer Inst 75: 303–306, 1985

    PubMed  Google Scholar 

  54. Cavanaugh PG, Nicolson GL: Isolation of a high molecular weight growth factor (LGF-1) for lung metastasizing mammary tumor cells from lung-conditioned media. Proc Am Assoc Cancer Res 29: 71, 1988

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Tumor Biology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, Texas, USA

    Garth L. Nicolson

Authors
  1. Garth L. Nicolson
    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

Nicolson, G.L. Differential organ tissue adhesion, invasion, and growth properties of metastatic rat mammary adenocarcinoma cells. Breast Cancer Res Tr 12, 167–176 (1988). https://doi.org/10.1007/BF01805938

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01805938

Key words

Search

Navigation