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Up-regulated Biosynthesis and Expression of Endothelial Cell Vitronectin Receptor Enhances Cancer Cell Adhesion¹

Departments of Pathology [R. M. L., T. J. P., M. R. B., F. W. O.], Medicine [T. J. P.], and Surgery [M. R. B.], McMaster University, Hamilton, Ontario, Canada

Extravasation of circulating cancer cells during metastasis is thought to involve adhesion to the vascular endothelium. To characterize this process, we measured the attachment of A549 human lung carcinoma cells to monolayers of cultured human umbilical vein endothelial cells. Pretreatment of the endothelial cells with 10 ng/ml interleukin 1 (IL-1) for 4 h increased cancer cell attachment 2–5-fold. This increase was blocked by 100 µM glycyl-arginyl-glycyl-aspartyl-serine peptide and was decreased 60 ± 10% (SD) by a vitronectin receptor polyclonal antiserum or 56 ± 8% by a vitronectin receptor monoclonal antibody, LM609. Glycyl-arginyl-glycyl-aspartyl-serine or the vitronectin receptor antibodies did not inhibit cancer cell attachment to untreated endothelial cells. A fibronectin receptor antiserum had no effect on attachment to untreated or IL-1-treated endothelial cells. Pretreatment of endothelial cells with IL-1 increased their adhesion to fibronectin and vitronectin and increased the expression of vitronectin receptor and fibronectin receptor as detected by immunofluorescence flow cytometry, quantitative antibody binding, and immunoprecipitation of [³⁵S]methionine-labeled cell extracts. IL-1 pretreatment also increased ß₁, ß₃, and _v integrin mRNA. The A549 cells did not express vitronectin receptor, since LM609 did not inhibit A549 adhesion to vitronectin or bind to A549 cells in flow cytometry, and vitronectin receptor antisera failed to immunoprecipitate vitronectin receptor from A549 cells. Furthermore, the ß₃ complementary DNA probe failed to hybridize to A549 RNA. A549 cells did express fibronectin receptor, which was increased by IL-1 treatment. We conclude that IL-1 induces the expression of both vitronectin receptor and fibronectin receptor on endothelial cells and that vitronectin receptor, in turn, facilitates A549 cell adhesion to endothelial cells.

¹ Supported by the Medical Research Council of Canada and the National Cancer Institute of Canada.

² To whom requests for reprints should be addressed, at Department of Pathology, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada, L8N 3Z3.

Received 8/28/91. Accepted 2/ 7/92.

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