ONCOSTATIN-M IS AN AUTOCRINE GROWTH-FACTOR IN KAPOSIS-SARCOMA

Oncostatin-M is a cytokine produced by macrophages and activated T lym phocytes that has recently been shown to be a mitogen for AIDS-related Kaposi's sarcoma (KS)derived spindle cells. The significance of oncos tatin-M production in AIDS-related KS in vivo, however, remains unknow n. In this study we wanted to determine whether oncostatin-M is expres sed in vivo in patients with HIV-I-related KS, define the cell types t hat express this cytokine, and compare with the control tissues from H IV-I-negative individuals. A second objective of our study was to defi ne the expression of oncostatin-M in AIDS-KS-derived spindle cell isol ates cultured in vitro and to determine whether oncostatin-M is an aut ocrine growth factor for these KS cells. The have determined that onco statin-M is not expressed in any of the several organs examined in con trol cases, whereas the tumor tissue obtained from the skin biopsies o f HIV-I-infected cases with KS displayed oncostatin-M expression in th e spindle cell components of the tumor, as well as the cells lining th e vascular structures, smooth muscle cells lining the eccrine sweat gl ands, and the epidermal layers ofthe skin. Furthermore, uninvolved ski n of patients with NN-related KS express oncostatin-M in the cells lin ing normal vessels. The mRNA polymerase chain reaction analysis confir med findings in the primary tissues and shouted expression in all of t he AIDS-KS-derived spindle cell isolates examined We have also shown w ith the use of oncostatin-M-specific antisense oligodeoxynucleotides t hat KS cell proliferation is inhibited, which correlated with a more p recipitous decline in the production of interleukin-6 by these cells. We conclude that oncostatin-M is only expressed in the skin and KS tum or of HN-I-infected individuals. Furthermore, we provide evidence that oncostatin-M is an autocrine growth factor for KS.