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. 1983 Nov;80(22):6863–6867. doi: 10.1073/pnas.80.22.6863

Monoclonal antibodies that prevent adhesion of B 16 melanoma cells and reduce metastases in mice: crossreaction with human tumor cells.

H P Vollmers, W Birchmeier
PMCID: PMC390086  PMID: 6316331

Abstract

Monoclonal antibodies raised against B 16 melanoma cells in syngeneic mice were functionally screened for their ability to inhibit cell adhesion in tissue culture. Three of these antibodies (16/43, 16/77, 16/82), when preinjected into C57BL/6 mice, markedly reduced the number of experimental lung metastases produced by B 16 cells, possibly by interference with their adhesion to the lung endothelia. We now report that these monoclonal antibodies block in vitro attachment of the majority of human melanoma cell lines tested and also of carcinoma, neuroblastoma, and glioblastoma cells from both mice and humans but untransformed cell lines such as 3T3 mouse or MRC-5 human fibroblasts are not affected. The antibodies also react with mouse teratocarcinoma stem cells (F9, PCC4) but not with differentiated teratocarcinoma lines (PYS-2, 944). Furthermore, the antiadhesion activity of the antibodies could be quantitatively absorbed by intact human and mouse tumor cells but not by untransformed cells, suggesting that the corresponding antigens may represent tumor-associated cell surface components. Correspondingly, the antigens were found on simian virus 40-transformed 3T3 mouse fibroblasts and are expressed in a temperature-sensitive fashion in chicken fibroblasts transformed with a temperature-sensitive Rous sarcoma virus. On "immunoblots" of NaDodSO4-containing gels the three selected antibodies (16/43, 16/82, 19/1) were absorbed by antigens with molecular weights of 40,000 and 50,000.

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Selected References

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  1. Bernstein I. D., Tam M. R., Nowinski R. C. Mouse leukemia: therapy with monoclonal antibodies against a thymus differentiation antigen. Science. 1980 Jan 4;207(4426):68–71. doi: 10.1126/science.6965328. [DOI] [PubMed] [Google Scholar]
  2. Bumol T. F., Wang Q. C., Reisfeld R. A., Kaplan N. O. Monoclonal antibody and an antibody-toxin conjugate to a cell surface proteoglycan of melanoma cells suppress in vivo tumor growth. Proc Natl Acad Sci U S A. 1983 Jan;80(2):529–533. doi: 10.1073/pnas.80.2.529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bystryn J. C., Jacobsen J. S., Liu P., Heaney-Kieras J. Comparison of cell-surface human melanoma-associated antigens identified by rabbit and murine antibodies. Hybridoma. 1982;1(4):465–472. doi: 10.1089/hyb.1.1982.1.465. [DOI] [PubMed] [Google Scholar]
  4. Carrel S., Schreyer M., Schmidt-Kessen A., Mach J. P. Reactivity spectrum of 30 monoclonal antimelanoma antibodies to a panel of 28 melanoma and control cell lines. Hybridoma. 1982;1(4):387–397. doi: 10.1089/hyb.1.1982.1.387. [DOI] [PubMed] [Google Scholar]
  5. Dippold W. G., Lloyd K. O., Li L. T., Ikeda H., Oettgen H. F., Old L. J. Cell surface antigens of human malignant melanoma: definition of six antigenic systems with mouse monoclonal antibodies. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6114–6118. doi: 10.1073/pnas.77.10.6114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Harper J. R., Bumol T. F., Reisfeld R. A. Serological and biochemical analyses of monoclonal antibodies to human melanoma-associated antigens. Hybridoma. 1982;1(4):423–432. doi: 10.1089/hyb.1.1982.1.423. [DOI] [PubMed] [Google Scholar]
  7. Hellström I., Brown J. P., Hellström K. E. Workshop on monoclonal antibodies to human melanoma-associated antigens: findings of the Seattle group. Hybridoma. 1982;1(4):399–402. doi: 10.1089/hyb.1.1982.1.399. [DOI] [PubMed] [Google Scholar]
  8. Herlyn D. M., Steplewski Z., Herlyn M. F., Koprowski H. Inhibition of growth of colorectal carcinoma in nude mice by monoclonal antibody. Cancer Res. 1980 Mar;40(3):717–721. [PubMed] [Google Scholar]
  9. Herlyn D., Koprowski H. IgG2a monoclonal antibodies inhibit human tumor growth through interaction with effector cells. Proc Natl Acad Sci U S A. 1982 Aug;79(15):4761–4765. doi: 10.1073/pnas.79.15.4761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Imai K., Molinaro G. A., Ferrone S. Monoclonal antibodies to human melanoma-associated antigens. Transplant Proc. 1980 Sep;12(3):380–383. [PubMed] [Google Scholar]
  11. Johnson J. P., Demmer-Dieckmann M., Meo T., Hadam M. R., Riethmüller G. Surface antigens of human melanoma cells defined by monoclonal antibodies. I. Biochemical characterization of two antigens found on cell lines and fresh tumors of diverse tissue origin. Eur J Immunol. 1981 Oct;11(10):825–831. doi: 10.1002/eji.1830111015. [DOI] [PubMed] [Google Scholar]
  12. Kantor R. R., Ng A. K., Giacomini P., Ferrone S. Analysis of the NIH workshop monoclonal antibodies to human melanoma antigens. Hybridoma. 1982;1(4):473–482. doi: 10.1089/hyb.1.1982.1.473. [DOI] [PubMed] [Google Scholar]
  13. Knowles M. A., Franks L. M. Stages in neoplastic transformation of adult epithelial cells by 7,12-dimethylbenz(a)anthracene in vitro. Cancer Res. 1977 Nov;37(11):3917–3924. [PubMed] [Google Scholar]
  14. Koprowski H., Steplewski Z., Herlyn D., Herlyn M. Study of antibodies against human melanoma produced by somatic cell hybrids. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3405–3409. doi: 10.1073/pnas.75.7.3405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Krolick K. A., Uhr J. W., Vitetta E. S. Selective killing of leukaemia cells by antibody-toxin conjugates: implications for autologous bone marrow transplantation. Nature. 1982 Feb 18;295(5850):604–605. doi: 10.1038/295604a0. [DOI] [PubMed] [Google Scholar]
  16. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  17. Lane E. B., Goodman S. L., Trejdosiewicz L. K. Disruption of the keratin filament network during epithelial cell division. EMBO J. 1982;1(11):1365–1372. doi: 10.1002/j.1460-2075.1982.tb01324.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Levine A. J. Transformation-associated tumor antigens. Adv Cancer Res. 1982;37:75–109. doi: 10.1016/s0065-230x(08)60882-9. [DOI] [PubMed] [Google Scholar]
  19. Miller R. A., Maloney D. G., McKillop J., Levy R. In vivo effects of murine hybridoma monoclonal antibody in a patient with T-cell leukemia. Blood. 1981 Jul;58(1):78–86. [PubMed] [Google Scholar]
  20. Miller R. A., Maloney D. G., Warnke R., Levy R. Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody. N Engl J Med. 1982 Mar 4;306(9):517–522. doi: 10.1056/NEJM198203043060906. [DOI] [PubMed] [Google Scholar]
  21. Nadler L. M., Stashenko P., Hardy R., Kaplan W. D., Button L. N., Kufe D. W., Antman K. H., Schlossman S. F. Serotherapy of a patient with a monoclonal antibody directed against a human lymphoma-associated antigen. Cancer Res. 1980 Sep;40(9):3147–3154. [PubMed] [Google Scholar]
  22. Oesch B., Birchmeier W. New surface component of fibroblast's focal contacts identified by a monoclonal antibody. Cell. 1982 Dec;31(3 Pt 2):671–679. doi: 10.1016/0092-8674(82)90322-1. [DOI] [PubMed] [Google Scholar]
  23. Ritz J., Pesando J. M., Sallan S. E., Clavell L. A., Notis-McConarty J., Rosenthal P., Schlossman S. F. Serotherapy of acute lymphoblastic leukemia with monoclonal antibody. Blood. 1981 Jul;58(1):141–152. [PubMed] [Google Scholar]
  24. Ross A. H., Mitchell K. F., Steplewski Z., Koprowski H. Identification and isolation of melanoma-associated antigens with monoclonal antibodies. Hybridoma. 1982;1(4):413–421. doi: 10.1089/hyb.1.1982.1.413. [DOI] [PubMed] [Google Scholar]
  25. Saxton R. E., Mann B. D., Morton D. L., Burk M. W. Monoclonal antibodies to 125 kd and 95 kd proteins on human melanoma cells: comparison with other monoclonal-defined melanoma antigens. Hybridoma. 1982;1(4):433–445. doi: 10.1089/hyb.1.1982.1.433. [DOI] [PubMed] [Google Scholar]
  26. Scheinberg D. A., Strand M., Gansow O. A. Tumor imaging with radioactive metal chelates conjugated to monoclonal antibodies. Science. 1982 Mar 19;215(4539):1511–1513. doi: 10.1126/science.7199757. [DOI] [PubMed] [Google Scholar]
  27. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Vollmers H. P., Birchmeier W. Monoclonal antibodies inhibit the adhesion of mouse B 16 melanoma cells in vitro and block lung metastasis in vivo. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3729–3733. doi: 10.1073/pnas.80.12.3729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Woodbury R. G., Brown J. P., Yeh M. Y., Hellström I., Hellström K. E. Identification of a cell surface protein, p97, in human melanomas and certain other neoplasms. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2183–2187. doi: 10.1073/pnas.77.4.2183. [DOI] [PMC free article] [PubMed] [Google Scholar]

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