Interactions between tumour cells and the endothelium are vital to the formation of haematogenous metastases. Binding to model endothelium of one oestrogen receptor positive breast carcinoma cell line (MCF-7) and one receptor negative line (HS578T) was examined in vitro together with endothelial retraction induced by these tumour cells. Adhesion was inhibited by monoclonal antibodies specific for the VLA integrins and by peptides containing the RGD motif which is commonly recognised as a ligand by the VLA adhesion molecules. However, binding of the two tumour cell lines was inhibited by monoclonal antibodies specific for different VLA molecules; anti-α6β1 inhibited MCF-7 adhesion but anti-α5β1 inhibited Hs578T. These results were consistent with flow cytometric quanfication of the expression of these VLA integrins on the surfaces of the two tumour cell lines. Enzyme-linked immunosorbent assays (ELISA) demonstrated that laminin was present on the endothelial cell surface but collagen IV was absent. ELISA failed to detect increased exposure of the subendothelial matrix during the first hour after addition of either cancer cell type. This was supported by assays which demonstrated maintenance of the endothelial permeability barrier during this period. Slight endothelial retraction was detected within 2 hours of the addition of tumour cells. It is concluded that binding between tumour cells and confluent endothelium is inhibited by the blockade of adhesion molecules which are normally associated with interactions between the cell and the subendothelial matrix. Tumour cell to matrix interactions rather than direct tumour to endothelial cell adhesion may be the limiting step in tumour cell binding to the endothelium.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Hart IR and Saini A, 1992, Biology of tumour metastasis. Lancet, 339, 1453–7.
Hart IR, Goode, NT and Wilson RE, 1989, Molecular aspects of the metastatic cascade. Biochim Biophys Acta, 989, 65–84.
Blood CH and Zetter BR, 1990, Tumor interactions with the vasculature: angiogenesis and tumor metastasis. Biochem Biophys Acta, 1032, 89–118.
McCarthy JB, Skubitz APN, Iida J et al, 1991, Tumor cell adhesive mechanisms and their relationship to metastasis. Sent Cancer Biol, 2, 155–67.
Plantefaber LC and Hynes RO, 1989, Changes in integrin receptors in oncogenically transformed cells. Cell, 56, 281–90.
Lauri D, Martin-Padura I, Bionelli T et al, 1991, Role of β1 integrins in tumor cell adhesion to cultured human endothelial cells. Lab Invest, 65, 525–32.
Johnson JP, 1991, Cell adhesion molecules of the immunoglobulin supergene family and their role in malignant transformation and progression to metastatic disease. Cancer Metastasis Rev, 10, 11–22.
Rasbridge SA, Gillett CE, Sampson SA, Walsh FS and Millis RR, 1993, Epithelial (E-) and placental (P-) cadherin cell adhesion molecule expression in breast carcinoma. J Pathol, 169, 245–50.
Zutter MM, Krigman HR and Santoro SA, 1993, Altered integrin expression in adenocarcinoma of the breast. Analysis by in situ hybridization. Am J Pathol, 142, 1439–48.
Ruoslahti E and Piersbacher MD, 1987, New perspectives in cell adhesion: RGD and integrins. Science, 238, 491–7.
Albelda SM and Buck CA, 1990, Integrins and other cell adhesion molecules. FASEB J, 4, 2868–80.
Hynes RO, Marcantonio EE, Stepp MA, Urry A and Yee GH, 1989, Integrin heterodimer and receptor complexity in avian and mammalian cells. J Cell Biol, 109, 409–20.
Palmer EL, Ruegg C, Ferrando R, Pytela R and Sheppard D, 1993, Sequence and tissue distribution of the integrin alpha 9 subunit, a novel partner of beta 1 that is widely distributed in epithelia and muscle. J Cell Biol, 123, 1289–97.
Larjava H, Peltonen J, Akiyama SK et al, 1990, Novel function for β1 integrins in keratinocyte cell-cell interactions. J Cell Biol, 110, 803–15.
Symington BE, Takada Y and Carter WG, 1993, Interaction of integrins alpha 3 and alpha 2 beta 1: potential role in keratinocyte intercellular adhesion. J Cell Biol, 120, 523–35.
Kaufmann R, Frosch D, Westphal C, Weber L and Klein CE, 1989, Integrin VLA-3: ultrastructural localization at cell-cell contact sites of human cell cultures. J Cell Biol, 109, 1807–15.
Saiki I, Murata J, Matsuno K et al, 1990, Anti-metastatic and anti-invasive effects of polymeric Arg-Gly-Asp (RGD) peptide, poly(RGD), and its analogues. Jpn J Cancer Res, 81, 660–7.
Gehlson KR, Argraves WS, Piersbacher MD and Ruoslahti E, 1988, Inhibition of in vitro tumor cell invasion by Arg-Gly-Asp-containing synthetic peptides. J Cell Biol, 106, 925–30.
Hardan I, Weiss L, Hershkoviz R et al, 1993, Inhibition of metastatic cell colonization in murine lungs and tumor-induced morbidity by non-peptidic Arg-Gly-Asp mimetics. Int J Cancer, 55, 1023–8.
Edgell C-J, McDonald CC and Graham JB, 1983, Permanent cell line expressing human factor VIII-related antigen established by hybridization. Proc Natl Acad Sci USA, 80, 3734–7.
van Oost BA, Edgell C-JS, Hay CW and MacGillivray RTA, 1986, Isolation of a human von Willebrand factor cDNA from the hybrid endothelial cell line EA.hy926. Biochem Cell Biol, 64, 699–705.
Edgell C-JS, Haizlip JE, Bagnell R et al, 1990, Endothelium specific Weibel-Palade bodies in a continuous human cell line EA.hy926, In Vitro Cell Dev Biol, 26, 1167–72.
Suggs JE, Madden MC, Friedman M and Edgell C-JS, 1986, Prostacyclin expression by a continuous human cell line derived from vascular endothelium. Blood, 68, 825–9.
Emeiss JJ and Edgell C-JS, 1988, Fibrinolytic properties of a human endothelial hybrid cell line (EA.hy926). Blood, 71, 1669–75.
Brown KA, Vora A, Biggerstaff J et al, 1993, Application of an immortalized human endothelial cell line to the leukocyte:endothelial adherence assay. J Immunol Meth, 163, 13–22.
Page CS, Holloway N, Smith H, Yacoub M and Rose ML, 1994. Alloproliferative responses to purified CD4+ and CD8+ cells to endothelial cells in the absence of contaminating accessory cells. Transplant, 57, 1628–37.
Thompson EW, Paik S, Brunner N et al, 1992, Association of increased basement membrane invasiveness with absence of estrogen receptor and expression of vimentin in human breast cancer cell lines. J Cell Physiol, 150, 534–44.
van de Wiel-van Kemenade E, van Kooyk Y, de Boer AJ et al, 1992, Adhesion of T and B lymphocytes to extracellular matrix and endothelial cells can be regulated through the β subunit of VLA. J Cell Biol, 117, 461–70.
Ruoslahti E and Giancotti FG, 1989, Integrins and tumor cell dissemination. Cancer Cells, 1, 119–26.
Dedhar S, 1990, Integrins and tumor invasion. BioEssays, 12, 583–90.
Juliano RL and Varner JA, 1993, Adhesion molecules in cancer: the role of integrins. Current Opin Cell Biol, 5, 812–8.
Lauri D, Martin-Padura I, Biondelli T et al, 1991, Role of β1 integrins in tumor cell adhesion to cultured human endothelial cells. Lab Invest, 65, 525–31.
Rothlein R and Springer TA, 1986, The requirement for lymphocyte function-associated antigen-1 in homotypic leukocyte adhesion stimulated by phorbol ester. J Exp Med, 163, 1132–49.
Hunes RO, 1992, Integrins: versatility, modulation, and signalling in cell adhesion. Cell, 69, 1:1–25.
Shimizu Y and Mobley JL, 1993, Distinct divalent cation requirements for integrin-mediated CD4+ve T lymphocyte adhesion to ICAM-1, fibronectin, VCAM-1, and invasin. J Immunol, 151, 4106–15.
Chen Y, Suri AK, Kominos D et al, 1994, 3-Dimensional structure of Echistatin and the dynamics of the active site. J Biomolec NMR, 4, 307–24.
D'Ardenne AJ, Richman PI, Horton MA, McAulay AE and Jordan S, 1991, Co-ordinate expression of the alpha-6 integrin laminin receptor sub-unit and laminin in breast cancer. J Pathol, 165, 213–20.
Giancotti FG and Ruoslahti E, 1990, Elevated levels of the α5β1 fibronectin receptor suppress the transformed phenotype of Chinese hamster ovary cells. Cell, 60, 849–59.
Takeuchi K, Tsuji T, Hakomori S and Irimura T, 1994, Intercellular adhesion induced by anti-α3 integrin (VLA-3) antibodies. Exp Cell Res, 211, 133–41.
Rotella CM, Galli G, Casisi A et al, 1993, Release of extracellular matrix components by bovine bone endothelial cells in continuous culture. Biochem Biophys Res Commun, 190, 502–8.
Yoshioka K, Mukai M, Shinkai K and Akedo H, 1993, Retraction of cultured endothelial cell monolayer by human breast cancer cells MCF-7. Cell Biol Internat, 17, 1053–63.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bliss, R.D., Kirby, J.A., Browell, D.A. et al. The role of β1 1 integrins in adhesion of two breast carcinoma cell lines to a model endothelium. Clin Exp Metast 13, 173–183 (1995). https://doi.org/10.1007/BF00132205
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00132205