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The role of E-cadherin and scatter factor in tumor invasion and cell motility

  • Chapter
Cell Motility Factors

Part of the book series: Experientia Supplementum ((EXS,volume 59))

Summary

The acquisition of invasive properties by transformed epithelial cells constitutes an essential step in the progression of carcinomas. We have defined 2 types of interferences leading to enhanced motility and invasiveness of epithelial cells: (i) disturbances of intercellular adhesion, and (ii) treatment with “scatter factor”, a secretory protein of mesenchymal cells. Invasive properties (invasion of collagen gels or embryonal heart tissue) are acquired by epithelial cells in vitro when intercellular adhesion is inhibited by antibodies that are specific for the cell-cell adhesion molecule E-cadherin. Furthermore, we found that differentiated human carcinoma cell lines are noninvasive and express E-cadherin, whereas dedifferentiated carcinoma lines are invasive and have lost E-cadherin expression. Invasiveness of these latter cells could be prevented by transfection with E-cadherin cDNA and was again induced by treatment of the transfected cells with anti-E-cadherin antibodies. A correlation between the degree of tumor differentiation and the amount of E-cadherin expression was also visualized on frozen sections of ovarian carcinomas, lobular breast carcinomas, and squamous carcinomas of head and neck. Thus, loss of E-cadherin appears to be a critical step in the establishment of an invasive, i.e. fully malignant phenotype. Scatter factor, which is also capable of dissociating epithelial cell colonies in vitro, was isolated from conditional medium of human fibroblasts; it is a 92,000 mol.wt glycoprotein, which is proteolytically cleaved into 62,000 and 34/32,000 mol.wt subunits. The purified glycoprotein induces invasion of MDCK cells into collagen matrices, and induces or enhances the invasive properties of various human carcinoma cell lines. Sequencing of tryptic peptides of scatter factor revealed strong similarity with hepatocyte growth factor. Furthermore, both factors exhibit identical activities, i.e. scatter factor stimulates DNA synthesis of primary hepatocytes and hepatocyte growth factor dissociates and increases the motility of various epithelial cells. Thus scatter factor and hepatocyte growth factor represent identical or closely similar proteins.

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References

  • Almoguera, C., Shibata, D., Forrester, K., Martin, J., Amheim, N., and Perucho, M. (1988) Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 53: 549–554.

    Article  Google Scholar 

  • Behrens, J., Birchmeier, W., Goodman, S. L., and Imhof, B. A. (1985) Dissociation of Madin-Darby canine kidney epithelial cells by the monoclonal antibody anti-Arc-1: Mechanistic aspects and identification of the antigen as a component related to uvomorulin. J. Cell. Biol. 101: 1307–1315.

    Article  Google Scholar 

  • Behrens, J., Mareel, M. M., Van Roy, F. M., and Birchmeier, W. (1989) Dissecting tumor cell invasion: Epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion. J. Cell Biol. 108: 2435–2447.

    Article  Google Scholar 

  • Behrens, S. J. and Birchmeier, W. (1990) Specific activity of the Arc-1/uvomorulin promoter in epithelial cells. 30th Annual Meeting of the American Society for Cell Biology 157a.

    Google Scholar 

  • Bertolotti, R., Rutishauser, U., and Edelman, G. (1980) A cell surface molecule involved in aggregation of embryonic liver cells. Proc. Natl. Acad. Sci. USA 77: 4831–4835.

    Article  Google Scholar 

  • Boiler, K., Vestweber, D., and Kemler, R. (1985) Cell-adhesion molecule uvomorulin is localized in the intermediate junctions of adult intestinal epithehal cells. J. Cell. Biol. 100: 327–332.

    Article  Google Scholar 

  • Bos, J. L., Fearon, E. R., Hamilton, S. R., Verlaan-De Vries, M., Van Boom, J. H., Van der Eb, A. J., and Vogelstein, B. (1987) Prevalence of ras gene mutations in human colorectal cancers. Nature 327: 293–297.

    Article  Google Scholar 

  • Damsky, C. H., Richa, J., Solter, D., Knudsen, K., and Buck, C. A. (1983) Identification and purification of a cell surface glycoprotein mediating intercellular adhesion in embryonic and adult tissue. Cell 34: 455–466.

    Article  Google Scholar 

  • Edelman, G. M., Gallin, W. J., Delouvee, A., Cunningham, B. A., and Thiery, J.-P. (1983) Early epochal maps of two different cell adhesion molecules. Proc. Natl. Acad. Sci. USA 80: 4384–4388.

    Article  Google Scholar 

  • Engel, L. W. and Young, N. A. (1978) Human breast carcinoma cells in continuous culture: A review. Cancer Res. 38: 4327–4339.

    Google Scholar 

  • Fearon, E. R., and Vogelstein, B. (1990) A genetic model for colorectal tumorigenesis. Cell 61: 759–767.

    Article  Google Scholar 

  • Finlay, C. A., Hinds, P. W., Tau, T.-H., Eliyahn, D., Oren, M., and Levine, A. J. (1989) Activating mutations for transformation by p53 produce a gene product that form an hsc 70-p53 complex with an altered half-life. Mol. Cell. Biol. 8: 531–539.

    Google Scholar 

  • Frixen, U., Behrens, J., Sachs, M., Eberle, G., Voss, B., Warda, A., Löchner, D., and Birchmeier, W. (1991) Arc-l/uvomorulin expression in differentiated and dedifferentiated human carcinoma cell lines: Correlation with invasion in vitro. J. Cell Biol., 113: 173–185.

    Article  Google Scholar 

  • Gabbert, H., Wagner, R., Moll, R., and Gerharz, C.-D. (1985) Tumor dedifferentiation: An important step in tumor invasion. Clin. Exp. Metastasis 3: 257–279.

    Article  Google Scholar 

  • Gallin, W. J., Edelman, G. M., and Cunningham, B. A. (1983) Characterization of L-CAM, a major cell adhesion molecule from embryonic liver cells. Proc. Natl. Acad. Sci. USA 80: 1038–1042.

    Article  Google Scholar 

  • Gallin, W. J., Sorkin, B. C., Edelman, G. M., and Cunningham, B. A. (1987) Sequence analysis of a cDNA clone encoding the liver cell adhesion molecule L-CAM. Proc. Natl. Acad. Sci. 84: 2808–2812.

    Article  Google Scholar 

  • Gessler, M., Pronstka, A., Cavenee, W., Neve, R. L., Orkin, S. H., and Bruns, G. A. P. (1990) Homozygous deletion in Wilm’s tumors of a zinc finger gene identified by chromosome jumping. Nature 343: 774–777.

    Article  Google Scholar 

  • Grey, A.-M., Schor, A. M., Rushton, G., Ellis, L, and Schor, S. L. (1989) Purification of the migration stimulating factor produced by fetal and breast cancer patient fibroblasts. Proc. Natl. Acad. Sci. U.S.A. 86: 2438–2442.

    Article  Google Scholar 

  • Haber, D. A., Buckler, A. J., Glaser, T., Call, K. M., Pelletier, J., Sohn, R. L., Douglass, E. C., and Housman, D. E. (1990) An internal deletion within an 11p13 zinc finger gene contributes to the development of Wilm’s tumor. Cell 61: 1257–1269.

    Article  Google Scholar 

  • Harbour, J., Lai, S., Whang-Peng, J., Gazdar, A., Minna, J., and Kaye, F. (1988) Abnormalities in structure and expression of the human retinoblastoma gene in SCLC. Science 241: 353–357.

    Article  Google Scholar 

  • Hashimoto, M., Niwa, O., Nitta, Y., Takeichi, M., and Yokoro, K. (1989) Unstable expression of E-cadherin molecules in metastatic ovarian tumor cells. Jpn. J. Cancer Res. 80: 459–463.

    Article  Google Scholar 

  • Hatta, K., Nose, A., Nagafuchi, A., and Takeichi, M. (1988) Cloning and expression of cDNA encoding a neural calcium-dependent cell adhesion molecule: Its identity in the Cadherin gene family. J. Cell. Biol. 106: 873–881.

    Article  Google Scholar 

  • Hyafil, F., Babinet, C., and Jacob, F. (1981) Cell-cell interactions in early embryogenesis: A molecular approach to the role of calcium. Cell 26: 447–454.

    Article  Google Scholar 

  • Imhof, B. A., Vollmers, H. P., Goodman, S. L., and Birchmeier, W. (1983) Cell-cell interaction and polarity of epithelial cells: Specific perturbation using a monoclonal antibody. Cell 35: 667–675.

    Article  Google Scholar 

  • Kok, K., Osinga, J., Carrit, B., Davis, M. B., Van der Hout, A. H., Van der Veen, A. Y., Landsvater, R. M., De Leij, L. F. M. H., Berendsen, H. H., Postmus, P. E., Poppema, S., and Buys, C. H. C. M. (1987) Deletion of DNA sequence at the chromosomal region 3p21 in all major types of lung cancer. Nature 330: 578–581.

    Article  Google Scholar 

  • Kovac, G., Erlandsson, R., Boldog, F., Ingvarsson, S., Müller-Bredlin, R., Klein, G., and Sümegi, J. (1988) Consistent chromosome 3p deletion and loss of heterozygosity in renal cell carcinoma. Proc. Natl. Acad. Sci. 85: 1571–1575.

    Article  Google Scholar 

  • Lee, E. Y.-H., To, H., Shew, J.-Y., Bookstein, R., Scully, P., and Lee, W.-H. (1988) Inactivation of the retinoblastoma susceptibility gene in human breast cancers. Science 241: 218–221.

    Article  Google Scholar 

  • Liotta, L. A., Mandler, R., Murano, G., Katz, D. A., Gordon, R. K., Ching, P. K., and Schiffmann, E. (1986a) Tumor cell autocrine motility factor. Proc. Natl. Acad. Sci. USA 83: 3302–3306.

    Article  Google Scholar 

  • Liotta, L. A., Rao, C. N., and Wewer, U. M. (1986b) Biochemical interactions of tumor cells with the basement membrane. Ann. Rev. Biochem. 55: 1037–1057.

    Article  Google Scholar 

  • Mege, R.-M., Matsuzaki, F., Gallin, W. J., Goldberg, J. I., Cunningham, B. A., and Edelman, G M. (1988) Construction of epithelioid sheets by transfection of mouse sarcoma cells with cDNAs for chicken cell adhesion molecules. Proc. Natl. Acad. Sci. USA 85: 7274–7278.

    Article  Google Scholar 

  • Mentges, B. (1987) Kolonkarzinom. Präoperatives CEA, Tumordifferenzierung und Prognose. Dtsch. Med. Wschr. 112: 1245–1249.

    Article  Google Scholar 

  • Miyazawa, K., Tsubouchi, H., Naka, D., Takahashi, K., Okigaki, M., Arakaki, N., Nakayama, H, Hirono, S., Sakiyama, O., Takahashi, K., Gohda, E., Daikuhara, Y., and Kitamura, N. (1989) Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor. Biochem. Biophys. Res. Commun. 163: 967–973.

    Article  Google Scholar 

  • Moll, R. (1986) Epithelial tumor markers. Verh. Dtsch. Ges. Pathol. 70: 28–50.

    Google Scholar 

  • Moll, R., Cowin, P., Kapprell, H.-P., and Franke, W. W. (1986) Biology of disease. Desmosomal proteins: New markers for identification and classification of tumors. Lab. Invest. 54: 4–25.

    Google Scholar 

  • Napfuchi, A., Shirayoshi, Y., Okazaki, K., Yasuda, K., and Takeichi, M. (1987) Transformation of cell adhesion properties by exogenously introduced E-cadherin cDNA. Nature 329: 341–343.

    Article  Google Scholar 

  • Nagafuchi, A., and Takeichi, M. (1988). Cell binding function of E-cadherin is regulated by the cytoplasmic domain. EMBO J. 7: 3679–3684.

    Google Scholar 

  • Nakamura, T., Nishizawa, T., Hagiya, M., Seki, T., Shimouishi, M., Sugimura, A., Tashiro, K., and Shimizu, S. (1989) Molecular cloning and expression of human hepatocyte growth factor. Nature 342: 440–443.

    Article  Google Scholar 

  • Natt, E., Mangenis, R. E., Zimmer, J., Mansouri, A., and Scherer, G. (1989). Regional assignment of the human loci for uvomorulin (UVO) and chymotrypsinogen B (CTRB) with the help of two overlapping deletions on the long arm of chromosome 16. Cytogen Cell Genet. 50: 145–148.

    Article  Google Scholar 

  • Nigro, J. M., Baker, S. J., Preisinger, A. C., Jessup, J. M., Hostetter, R., Cleary, K., Bigner, S. H., Davidson, N., Baylin, S., Devilee, P., Glover, T., Collins, F. S., Weston, A., Modah, R., Harris, C. C., and Vogelstein, B. (1989) Mutations in the p53 gene occur in diverse human tumor types. Nature 342: 705–708.

    Article  Google Scholar 

  • Osborn, M., and Weber, K. (1983) Tumor diagnosis by intermediate filament typing: A novel tool for surgical pathology. Lab. Invest. 48: 372–394.

    Google Scholar 

  • Ozawa, M., Baribault, H., and Kemler, R. (1989) The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins, structurally related in different species. EMBO J. 8: 1711–1717.

    Google Scholar 

  • Ozawa, M., Ringwald, M., and Kemler, R. (1990) Uvomorulin-catenin complex formation is regulated by a specific domain in the cytoplasmic version of the cell adhesion molecule. PNAS 87: 4246–4250.

    Article  Google Scholar 

  • Peyrieras, N., Hyafil, F., Louvard, D., Ploegh, H. L., and Jacob, F. (1983) Uvomorulin: A nonintegral membrane protein of early mouse embryo. Proc. Natl. Acad. Sci. USA 80: 6274–6277.

    Article  Google Scholar 

  • Pfisterer, J., Wintzer, O., Frixen, H., Behrens, J., Eberle, G., Birchmeier, W., and Bauknecht, T. (1990) Arc-1/uvomorulin by immunochemistry in non-malignant and in ovarian tumors. J. Cancer Res. Clin. Oncol. 116: 182.

    Google Scholar 

  • Ringwald, M., Schuh, R., Vestweber, D., Eistetter, H., Lottspeich, F., Engel, J., Dölz, R., Jähnig, F., Epplen, J., Mayer, S., Müller, C., and Kemler, R. (1987) The structure of the cell adhesion molecule uvomorulin. Insights into the molecular mechanism of Ca2+-dependent cell adhesion. EMBO J. 6: 3647–3653.

    Google Scholar 

  • Rosen, E. M. and Goldberg, I. D. (1989) Protein factors which regulate cell motility. In vitro Cell. Dev. Biol. 25: 1079–1087.

    Article  Google Scholar 

  • Shimoyama, Y., Yoshida, T., Terada, M., Shimosato, Y., Abe, O., and Hirohashi, S. (1989a) Molecular cloning of a human +-dependent cell-cell adhesion molecule homologous to mouse placental Cadherin: Its low expression in human placental tissue. J. Cell Biol. 109: 1787–1794.

    Article  Google Scholar 

  • Shimoyama, Y., Hirohashi, S., Hirano, S., Nogushi, M., Shimosata, Y., Takeichi, M., and Abe, O. (1989b) Cadherin cell-adhesion molecules in human epithehal tissues and carcinomas. Cancer Res. 49: 2128–2133.

    Google Scholar 

  • Shirayoshi, Y., Okada, T. S., and Takeichi, M. (1983) The calcium-dependent cell-cell adhesion system regulates inner cell mass formation and the cell surface polarization in early mouse development. Cell 35: 631–638.

    Article  Google Scholar 

  • Slamon, D. J., Godolphin, W., Jones, L. A., Holt, J. A, Wong, S. G., Keith, D. E., Levin, W. J., Stuart, S. G., Udove, L. J, Ullrich, A., and Press, M. F. (1989) Studies of the UER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244: 707–712.

    Article  Google Scholar 

  • Sorkin, B. C., Hemperly, J. J., Edelman, G., and Cunningham, B. A. (1988) Structure of the gene for the liver cell adhesion molecule, L-CAM. Proc. Natl. Acad. Sci. USA 85: 7617–7621.

    Article  Google Scholar 

  • Stoker, M., Gherardi, E., Perryman, M., and Gray, J. (1987) Scatter factor is a fibroblast-derived modulator of epithelial cell motility. Nature 327: 239–242.

    Article  Google Scholar 

  • Takahashi, T., Nau, M. M., Chiba, I., Birrer, M. J., Rosenberg, R. K., Vinocour, M., Levitt, M., Pass, H., Gazdar, A. F., and Minna, J. (1989) p53: A frequent target for genetic abnormalities in lung cancer. Science 246: 491–494.

    Article  Google Scholar 

  • Takeichi, M. (1988) The Cadherins: cell-cell adhesion molecules controUing animal morphogenesis. Development 102: 639–655.

    Google Scholar 

  • Tryggvason, K., Hoyhtyä, M., and Salo, T. (1987) Proteolytic degradation of extracellular matrix in tumor invasion. Biochim. Biophys. Acta 907: 191–217.

    Google Scholar 

  • Tsuda, H., Zhang, W., Shimosato, Y., Yokota, Y., Terada, M., Sugimura, T., Miyamura, T., and Hirohashi, S. (1990) Allele loss on chromosome 16 associated with progression of human hepatocellular carcinoma. Proc. Natl. Acad. Sci. USA 87: 6791–6794.

    Article  Google Scholar 

  • Vestweber, D., and Kemler, R. (1984) Rabbit antiserum against a purified surface glycoprotein decompacts mouse preimplantation embryos and reacts with specific adult tissues, Exp. Cell Res. 152: 169–178.

    Article  Google Scholar 

  • Weidner, K. M., Behrens, J., Vandekerckhove, J., and Birchmeier, W. (1990). Scatter factor: Molecular characteristics and effect on the invasion of epithehal cells. J. Cell Biol. 111: 2097–2108.

    Article  Google Scholar 

  • Weidner, K. M., Arakaki, N., Hartmann, G., Vandekerckhove, J., Weingart, S., Rieder, C., Fonatsch, H., Tsubouchi, H., Hishida, T., Daikuhara, Y., and Birchmeier, W. (1991) Evidence for the identity of human scatter factor and human hepatocyte growth factor. Proc. Natl. Acad. Sci. USA, in press.

    Google Scholar 

  • Weinstein, R. S., Merk, F. B., and Alroy, J. (1976) The structure and function of intercellular junctions in cancer. Adv. Cancer Res. 23: 23–89.

    Article  Google Scholar 

  • Zbar, B., Brauch, H., Talmadge, C., and Linehan, M. (1987) Loss of alleles of loci on the short arm of chromosome 3 in renal carcinoma. Nature 327: 721–725.

    Article  Google Scholar 

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Authors and Affiliations

  1. Institut für Zellbiologie (Tumorforschung), Universitätsklinikum, Virchowstrasse 173, D-4300, Essen 1, Germany

    Jürgen Behrens, K. Michael Weidner, Uwe H. Frixen, Jörg H. Schipper, Martin Sachs, Naokatu Arakaki, Yasushi Daikuhara & Walter Birchmeier

  2. Dept. of Biochemistry, Kagoshima University Dental School, Kagoshima 890, Japan

    Yasushi Daikuhara

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  1. Jürgen Behrens
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  2. K. Michael Weidner
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  3. Uwe H. Frixen
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  4. Jörg H. Schipper
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  5. Martin Sachs
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  6. Naokatu Arakaki
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  7. Yasushi Daikuhara
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  8. Walter Birchmeier
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  1. Department of Radiation Oncology, Long Island Jewish Medical Center, 270-05 76th Avenue, 11042, New Hyde Park, NY, USA

    I. D. Goldberg M.D.

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© 1991 Birkhäuser Verlag Basel/Switzerland

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Behrens, J. et al. (1991). The role of E-cadherin and scatter factor in tumor invasion and cell motility. In: Goldberg, I.D. (eds) Cell Motility Factors. Experientia Supplementum, vol 59. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7494-6_8

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  • DOI: https://doi.org/10.1007/978-3-0348-7494-6_8

  • Publisher Name: Birkhäuser Basel

  • Print ISBN: 978-3-0348-7496-0

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