Distinct CXC chemokines mediate tumorigenicity of prostate cancer cells

Prostate cancer is the second leading cause of malignancy-related mortality in males in the United States. As a solid tumor, clinically significant tu mor growth and metastasis are dependent on nutrients and oxygen supplied by tumor-associated neovasculature. As such, there is a selective tumorigenic advantage for those neoplasms that can produce angiogenic mediators. We sh ow here that human prostate cancer cell Lines can constitutively produce an giogenic CXC chemokines, Tumorigenesis of PC-3 prostate cancer cells was sh own to be attributable, in part, to the production of the angiogenic CXC ch emokine, interleukin (IL)-8. Neutralizing antisera to IL-8 inhibits PC-3 tu mor growth in a human prostate cancer/SCID mouse model. Furthermore, angiog enic activity in PC-3 tumor homogenates was attributable to IL-8, In contra st, the Du145 prostate cancer cell line uses a different angiogenic CXC che mokine, GRO-alpha, to mediate tumorigenicity, Neutralizing antisera to GRO- alpha but not IL-8 reduced tumor growth in vivo and reduced the angiogenic activity in tumor homogenates. Thus, prostate cancer cell Lines can use dis tinct CXC chemokines to mediate their tumorigenicity.