ENVIRONMENTAL INDUCTION OF TUMOR PHENOTYPE IN A PUTATIVE KAPOSI-SARCOMA PROGENITOR-CELL

Many features of AIDS-related Kaposi sarcoma (AIDS-KS), e.g., multifoc al lesional presentation at sites perfused by the microvasculature, su ggest that AIDS-KS is initially a hyperplasia that subsequently progre sses to a neoplasia. We propose that the unique AIDS environment, whic h contains high levels of circulating factors such as viral cytokines, is key in initiating the KS lesion. Further, we maintain that due to their physiological function, human microvascular endothelial cells (H MECs) are both likely target cells for the AIDS-related cytokines, and are putative AIDS-KS progenitor cells. Previously we have shown that as a component of HMEC transition between proliferative and differenti ated growth, HMECs modulate their nucleotide and glutathione levels. A fter attaining contact inhibition, HMECs enter a state of differentiat ion, which is characterized by cellular entrance into a GO, quiescent growth state, a decrease in cellular bioenergetic profiles, and sponta neous formation of microtubules. In contrast, when cultured in a ''KS milieu'', HMECs fail to differentiate. Instead, the ''KS milieu'' cult ured cells assume a ''growth relaxed'' phenotype and demonstrate a lac k of contact inhibition, loss of anchorage dependence, and retention o f a ''proliferative'' bioenergetic profile despite culture confluence. Our results imply both that HMECs are responsive to AIDS-related cyto kines, and that the local environment is keg, to instigating a relaxat ion of cellular growth controls.