Early- and Late-Stage Kaposi's Sarcoma-Derived Cells But Not Activated Endothelial Cells Can Invade De-Epidermized Dermis

Abstract

Whether Kaposi's sarcoma is a true neoplasm or a reactive endothelial cell outgrowth triggered by inflammatory cytokines remains unclear. In this study, we investigated the differential invasive properties of activated endothelial cells and Kaposi's sarcoma cells in a model of de-epidermized dermis, supplying the cells with matrix barriers similar to those found in vivo. Cells derived from early "patch-stage" and from late "nodular-stage" Kaposi's sarcoma lesions exhibited similar invasive properties, which indicates that cells with an invasive potential are present in the early stages of tumor development. Slow accumulation of the cells into the extracellular matrix, together with a low proliferation index and with expression of anti-apoptotic proteins, suggest that the progression of Kaposi's sarcoma may be related to escape from cell death rather than to increased proliferation. The Kaposi's sarcoma-Y1 cell line, which is tumorigenic in nude mice, also exhibited invasive properties. By contrast to the Kaposi's sarcoma-derived spindle cells, however, which were scattered between the collagen bundles, the Kaposi's sarcoma-Y1 cell population had a higher proliferation index and displayed a multilayer arrangement. Inflammatory cytokines and Kaposi's sarcoma cell supernatant could activate and stimulate the growth of human dermal microvascular endothelial cell, but could not induce their invasion in this model, showing that activated endothelial cells do not fit all the requirements to traverse the various barriers found in the dermal extracellular matrix. 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.