Abstract
Malignant cells must traverse basement membranes during their migration to sites distant from the primary tumor. Since basement membranes are thought to be a critical barrier to the passage of tumor cells, we have constructed a model basement membrane-stromal matrix consisting of laminin and type IV collagen reconstituted onto a disk of type I collagen for use in an in vitro assay of invasiveness. Metastatic tumor cells and leukocytes are able to cross this barrier, whereas nonmetastatic tumor cells, fibroblasts, and epidermal cells cannot penetrate it. Those tumor cells that penetrate the barriers were found, when isolated and subcultured, to be more invasive and to produce more metastases than the parental population. This assay system should be useful for studying the invasiveness of tumor cells and for isolating highly invasive variants.
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Selected References
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- Barsky S. H., Siegal G. P., Jannotta F., Liotta L. A. Loss of basement membrane components by invasive tumors but not by their benign counterparts. Lab Invest. 1983 Aug;49(2):140–147. [PubMed] [Google Scholar]
- Easty D. M., Easty G. C. Measurement of the ability of cells to infiltrate normal tissues in vitro. Br J Cancer. 1974 Jan;29(1):36–49. doi: 10.1038/bjc.1974.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fidler I. J. Selection of successive tumour lines for metastasis. Nat New Biol. 1973 Apr 4;242(118):148–149. doi: 10.1038/newbio242148a0. [DOI] [PubMed] [Google Scholar]
- Foidart J. M., Bere E. W., Jr, Yaar M., Rennard S. I., Gullino M., Martin G. R., Katz S. I. Distribution and immunoelectron microscopic localization of laminin, a noncollagenous basement membrane glycoprotein. Lab Invest. 1980 Mar;42(3):336–342. [PubMed] [Google Scholar]
- Giavazzi R., Alessandri G., Spreafico F., Garattini S., Mantovani A. Metastasizing capacity of tumour cells from spontaneous metastases of transplanted murine tumours. Br J Cancer. 1980 Sep;42(3):462–472. doi: 10.1038/bjc.1980.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hart I. R., Fidler I. J. The implications of tumor heterogeneity for studies on the biology of cancer metastasis. Biochim Biophys Acta. 1981 Aug 31;651(1):37–50. doi: 10.1016/0304-419x(81)90004-4. [DOI] [PubMed] [Google Scholar]
- Hart I. R. The selection and characterization of an invasive variant of the B16 melanoma. Am J Pathol. 1979 Dec;97(3):587–600. [PMC free article] [PubMed] [Google Scholar]
- Hujanen E. S., Terranova V. P. Migration of tumor cells to organ-derived chemoattractants. Cancer Res. 1985 Aug;45(8):3517–3521. [PubMed] [Google Scholar]
- Klebe R. J. Isolation of a collagen-dependent cell attachment factor. Nature. 1974 Jul 19;250(463):248–251. doi: 10.1038/250248a0. [DOI] [PubMed] [Google Scholar]
- Kleinman H. K., McGarvey M. L., Liotta L. A., Robey P. G., Tryggvason K., Martin G. R. Isolation and characterization of type IV procollagen, laminin, and heparan sulfate proteoglycan from the EHS sarcoma. Biochemistry. 1982 Nov 23;21(24):6188–6193. doi: 10.1021/bi00267a025. [DOI] [PubMed] [Google Scholar]
- Liotta L. A., Abe S., Robey P. G., Martin G. R. Preferential digestion of basement membrane collagen by an enzyme derived from a metastatic murine tumor. Proc Natl Acad Sci U S A. 1979 May;76(5):2268–2272. doi: 10.1073/pnas.76.5.2268. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liotta L. A., Lee C. W., Morakis D. J. New method for preparing large surfaces of intact human basement membrane for tumor invasion studies. Cancer Lett. 1980 Dec;11(2):141–152. doi: 10.1016/0304-3835(80)90105-6. [DOI] [PubMed] [Google Scholar]
- Liotta L. A., Rao C. N., Barsky S. H. Tumor invasion and the extracellular matrix. Lab Invest. 1983 Dec;49(6):636–649. [PubMed] [Google Scholar]
- Liotta L. A., Thorgeirsson U. P., Garbisa S. Role of collagenases in tumor cell invasion. Cancer Metastasis Rev. 1982;1(4):277–288. doi: 10.1007/BF00124213. [DOI] [PubMed] [Google Scholar]
- Liotta L. A., Tryggvason K., Garbisa S., Hart I., Foltz C. M., Shafie S. Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature. 1980 Mar 6;284(5751):67–68. doi: 10.1038/284067a0. [DOI] [PubMed] [Google Scholar]
- Liotta L. A. Tumor invasion and metastases: role of the basement membrane. Warner-Lambert Parke-Davis Award lecture. Am J Pathol. 1984 Dec;117(3):339–348. [PMC free article] [PubMed] [Google Scholar]
- Malinoff H. L., Wicha M. S. Isolation of a cell surface receptor protein for laminin from murine fibrosarcoma cells. J Cell Biol. 1983 May;96(5):1475–1479. doi: 10.1083/jcb.96.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCarthy J. B., Palm S. L., Furcht L. T. Migration by haptotaxis of a Schwann cell tumor line to the basement membrane glycoprotein laminin. J Cell Biol. 1983 Sep;97(3):772–777. doi: 10.1083/jcb.97.3.772. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murray J. C., Liotta L., Rennard S. I., Martin G. R. Adhesion characteristics of murine metastatic and nonmetastatic tumor cells in vitro. Cancer Res. 1980 Feb;40(2):347–351. [PubMed] [Google Scholar]
- Nicolson G. L., Poste G. Tumor cell diversity and host responses in cancer metastasis--part I--properties of metastatic cells. Curr Probl Cancer. 1982 Dec;7(6):1–83. doi: 10.1016/s0147-0272(82)80017-2. [DOI] [PubMed] [Google Scholar]
- Nicolson G. L., Poste G. Tumor implantation and invasion at metastatic sites. Int Rev Exp Pathol. 1983;25:77–181. [PubMed] [Google Scholar]
- Poste G., Doll J., Hart I. R., Fidler I. J. In vitro selection of murine B16 melanoma variants with enhanced tissue-invasive properties. Cancer Res. 1980 May;40(5):1636–1644. [PubMed] [Google Scholar]
- Poste G. Experimental systems for analysis of the malignant phenotype. Cancer Metastasis Rev. 1982;1(2):141–199. doi: 10.1007/BF00048224. [DOI] [PubMed] [Google Scholar]
- Schleich A. B., Frick M., Mayer A. Patterns of invasive growth in vitro. Human decidua graviditatis confronted with established human cell lines and primary human explants. J Natl Cancer Inst. 1976 Feb;56(2):221–237. doi: 10.1093/jnci/56.2.221. [DOI] [PubMed] [Google Scholar]
- Terranova V. P., Liotta L. A., Russo R. G., Martin G. R. Role of laminin in the attachment and metastasis of murine tumor cells. Cancer Res. 1982 Jun;42(6):2265–2269. [PubMed] [Google Scholar]
- Terranova V. P., Rao C. N., Kalebic T., Margulies I. M., Liotta L. A. Laminin receptor on human breast carcinoma cells. Proc Natl Acad Sci U S A. 1983 Jan;80(2):444–448. doi: 10.1073/pnas.80.2.444. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Terranova V. P., Rohrbach D. H., Martin G. R. Role of laminin in the attachment of PAM 212 (epithelial) cells to basement membrane collagen. Cell. 1980 Dec;22(3):719–726. doi: 10.1016/0092-8674(80)90548-6. [DOI] [PubMed] [Google Scholar]
- Terranova V. P., Williams J. E., Liotta L. A., Martin G. R. Modulation of the metastatic activity of melanoma cells by laminin and fibronectin. Science. 1984 Nov 23;226(4677):982–985. doi: 10.1126/science.6505678. [DOI] [PubMed] [Google Scholar]
- Timpl R., Rohde H., Robey P. G., Rennard S. I., Foidart J. M., Martin G. R. Laminin--a glycoprotein from basement membranes. J Biol Chem. 1979 Oct 10;254(19):9933–9937. [PubMed] [Google Scholar]