Early- and late-stage Kaposi's sarcoma-derived cells but not activated endothelial cells can invade de-epidermized dermis

Whether Kaposi's sarcoma is a true neoplasm or a reactive endothelial cell outgrowth triggered by inflammatory cytokines remains unclear. In this stud y, we investigated the differential invasive properties of activated endoth elial cells and Kaposi's sarcoma cells in a model of de-epidermized dermis, supplying the cells with matrix barriers similar to those found ill vivo, Cells derived from early "patch-stage" and from late "nodular-stage" Kaposi 's sarcoma lesions exhibited similar invasive properties, which indicates t hat cells with an invasive potential are present in the early stages of tum or development. Slow accumulation of the cells into the extracellular matri x, together with a low proliferation index and with expression of anti-apop totic proteins, suggest that the progression of Kaposi's sarcoma may be rel ated to escape from cell death rather than to increased proliferation. The Kaposi's sarcoma-Y1 cell line, which is tumorigenic in nude mice, also exhi bited invasive properties. By contrast to the Kaposi's sarcoma-derived spin dle cells, however, which were scattered between the collagen bundles, the Kaposi's sarcoma-Y1 cell population had a higher proliferation index and di splayed a multilayer arrangement. Inflammatory cytokines and Kaposi's sarco ma cell supernatant could activate and stimulate the growth of human dermal microvascular endothelial cell, but could not induce their invasion in thi s model, showing that activated endothelial cells do not fit all the requir ements to traverse the various barriers found in the dermal extracellular m atrix. These results confer to Kaposi's sarcoma cells a tumor phenotype and suggest that the in vivo dominant endothelial cell population represents a reactive hyperplasia rather than the true tumor process.