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Significance of three-dimensional growth patterns of mammary tissues in collagen gels

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Five tumor cell lines that originated from a single mouse mammary adenocarcinoma, normal mammary tissue, a preneoplastic alveolar nodule line, and a tumor developing spontaneously from that preneoplastic line were used to study the different three-dimensional growth patterns that mammary tissues produce in collagen gel. We describe five different outgrowth morphologies, one of which may represent normal stromal tissue and infiltrating cells. One type was produced both by tumors and by normal mammary gland tissue in an age-related fashion, i.e. more outgrowths of this type were produced by mammary tissue from older mice. The outgrowth patterns for the tumor cell lines were not related to morphology in monolayer culture. Certain of the tumor lines, including one variant-producing line, produced multiple outgrowth patterns. Our results indicate that this cultivation technique may be a useful method for studying the heterogeneity of mammary tumors and may facilitate the isolation of mammary tumor subpopulations.

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References

  1. Emerman, J. T.; Enami, J.; Pitelka, D.; Nandi, S. Hormonal effect on intracellular and secreted casein in cultures of mouse mammary epithelial cells on floating collagen membranes. Proc. Natl. Acad. Sci. USA 74: 4466–4470; 1977.

    Article  PubMed  CAS  Google Scholar 

  2. Hallowes, R. C.; Bone, E. J.; Jones, W. A new dimension in the culture of human breast. Richards, R. J.; Rajan, K. T. eds. Tissue culture in medical research (II). Oxford: Pergamon Press; 1980: 213–220.

    Google Scholar 

  3. Yang, J.; Richards, J.; Bowman, P.; Guzman, R.; Enami, J.; McCormick, K.; Hamamoto, S.; Pitelka, D.; Nandi, S. Sustained growth and three-dimensional organization of primary tumor epithelial cells embedded in collagen gels. Proc. Natl. Acad. Sci. USA 76: 3401–3405; 1979.

    Article  PubMed  CAS  Google Scholar 

  4. Yang, N.-S.; Kube, D.; Park, C.; Furmanski, P. Growth of human mammary epithelial cells on collagen gel surfaces. Cancer Res. 41: 4093–4100; 1981.

    PubMed  CAS  Google Scholar 

  5. Yang, J.; Elias, J. J.; Petrakis, N. L.; Willings, S. R.; Nandi, S. Effects of hormones and growth factors on human mammary epithelial cells in collagen gel culture. Cancer Res. 41: 1021–1027; 1982.

    Google Scholar 

  6. Dexter, D. L.; Kowalski, H. M.; Blazar, B. A.; Fligiel, Z.; Vogel, R.; Heppner, G. H. Heterogeneity of tumor cells from a single mouse mammary tumor. Cancer Res. 38: 3174–3181; 1978.

    PubMed  CAS  Google Scholar 

  7. Heppner, G. H.; Dexter, D. L.; DeNucci, T.; Miller, F. R.; Calabresi, P. Heterogeneity in drug sensitivity among tumor cell subpopulations of a single mammary tumor. Cancer Res. 38: 3758–3763; 1978.

    PubMed  CAS  Google Scholar 

  8. Miller, F. R.; Heppner, G. H. Immunologic heterogeneity of tumor cell subpopulations from a single mouse mammary tumor. J. Natl. Cancer Inst. 63: 1457–1463; 1979.

    PubMed  CAS  Google Scholar 

  9. Miller, F. R.; Miller, B. E.; Heppner, G. H. Characterization of metastatic heterogeneity among subpopulations of a single mouse mammary tumor: Heterogeneity in phenotypic stability. Invasion Metastasis 3: 22–31; 1983.

    PubMed  CAS  Google Scholar 

  10. Hager, J. C.; Richardson, A. M.; Fligiel, S.; Heppner, G. H. Characterization of a variant-producing tumor cell line from a heterogeneous strain BALB/cfC3H mouse mammary tumor. Cancer Res. 41: 1293–1300; 1981.

    PubMed  CAS  Google Scholar 

  11. Medina, D. Preneoplastic lesions in mouse mammary cancer. Cancer Res. 36: 2589–2595; 1976.

    PubMed  CAS  Google Scholar 

  12. Schor, S. L. Cell proliferation and migration on collagen substrata in vitro. J. Cell Sci. 41: 159–175; 1980.

    PubMed  CAS  Google Scholar 

  13. Hager, J. C.; Russo, J.; Ceriani, R. L.; Peterson, J. A.; Fligiel, S.; Jolly, G.; Heppner, G. H. Epithelial characteristics of five subpopulations of a heterogeneous strain BALB/cfC3H mouse mammary tumor. Cancer Res. 41: 1720–1730; 1981.

    PubMed  CAS  Google Scholar 

  14. DeOme, K. B.; Miyamoto, M. J.; Osborn, R. C.; Guzman, R. C.; Lum, K. Detection of inapparent nodule-transformed cells in the mammary gland tissues of virgin female BALB/cfC3H mice. Cancer Res. 38: 2103–2111; 1978.

    PubMed  CAS  Google Scholar 

  15. Ormerod, E. J.; Rudland, P. S. Mammary gland morphogenesisin vitro: formation of branched tubules in collagen gels by a cloned rat mammary cell line. Dev. Biol. 91: 360–375; 1982.

    Article  PubMed  CAS  Google Scholar 

  16. Bennett, D. C.; Armstrong, B. L.; Okada, S. M. Reconstitution of branching tubules from two cloned mammary cell types in culture. Dev. Biol. 87: 193–199; 1981.

    Article  PubMed  CAS  Google Scholar 

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The investigations were supported by Public Health Service Grants CA 27437 and CA 28366 from the National Cancer Institute, Bethesda, MD, by the E. Walter Albachten bequest, and by the United Foundation of Greater Detroit.

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Lawler, E.M., Miller, F.R. & Heppner, G.H. Significance of three-dimensional growth patterns of mammary tissues in collagen gels. In Vitro 19, 600–610 (1983). https://doi.org/10.1007/BF02619573

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  • DOI: https://doi.org/10.1007/BF02619573

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