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Supernatants of Acquired Immunodeficiency Syndrome-related Kaposi's Sarcoma Cells Induce Endothelial Cell Chemotaxis and Invasiveness¹

Laboratory of Developmental Biology and Anomalies, National Institute of Dental Research [E. W. T., T. B. S., G. R. M.], and Laboratory of Tumor Cell Biology, National Cancer Institute [S. N., S. Z. S., R. C. G.], NIH, Bethesda, Maryland 20892, and Istituto Nazionale per la Ricerca sul Cancro, Viale Benedetto XV, 10, 16132 Genoa, Italy [A. A., A. M.]

Kaposi's sarcoma (KS) in general, and acquired immunodeficiency syndrome-related KS (AIDS-KS) in particular, is a highly invasive and intensely angiogenic neoplasm of unknown cellular origin. We have recently established AIDS-KS cells in long term culture and reported the development of KS-like lesions in nude mice inoculated with these cells. Here, we have examined the in vitro invasiveness of basement membrane by AIDS-KS cells, as well as the effect(s) of their supernatants on the migration and invasiveness of human vascular endothelial cells. AIDS-KS cells were highly invasive in the Boyden chamber invasion assay and formed invasive, branching colonies in a 3-dimensional gel (Matrigel). Normal endothelial cells form tube-like structures on Matrigel. AIDS-KS cell-conditioned media induced endothelial cells to form invasive clusters in addition to tubes. KS-cell-conditioned media, when placed in the lower compartment of the Boyden chamber, stimulated the migration of human and bovine vascular endothelial cells across filters coated with either small amounts of collagen IV (chemotaxis) or a Matrigel barrier (invasion). Basic fibroblast growth factor could also induce endothelial cell chemotaxis and invasion in these assays. However, when antibodies to basic fibroblast growth factor were used the invasive activity induced by the AIDS-KS-cell-conditioned media was only marginally inhibited, suggesting that the large quantities of basic fibroblast growth factor-like material released by the AIDS-KS cells are not the main mediators of this effect. Specific inhibitors of laminin and collagenase IV action, which represent critical determinants of basement membrane invasion, blocked the invasiveness of the AIDS-KS cell-activated endothelial cells in these assays. These data indicate that KS cells appear to be of smooth muscle origin but secrete a potent inducer of endothelial cell chemotaxis and invasiveness which could be responsible for angiogenesis and the resulting highly vascularized lesions. These assays appear to be a model to study the invasive spread and angiogenic capacity of human AIDS-related KS and should prove useful in the identification of molecular mediators and potential inhibitors of neoplastic neovascularization.

¹ This investigation was partially supported by a grant from the Ministero della Sanità, Progetto AIDS N. 5206 002.

² Present address: Department of Internal Medicine, University of California, Los Angeles, CA 90033.

³ To whom requests for reprints should be addressed.

Received 10/29/90. Accepted 3/ 8/91.

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