Proteomic signatures of angiogenesis in androgen‐independent prostate cancer

Abstract

The observation that angiogenesis, the process of new blood vessel formation, in healthy prostate and early prostate cancer is androgen-dependent gave rise to significant questions on how hypervascularization and increased angiogenesis is also achieved at the molecular level in advanced androgen-independent prostate cancer. The exact paracrine molecular network that is hardwired into the proteome of the endothelial and cancer subpopulations participating in this process remains partially understood. Here, we interrogated the signaling pathways and the molecular functional signatures across the proteome of endothelial cells after interacting with various secretomes produced by androgen-dependent and -independent prostate cancer cells. We found the significant overexpression (P < 0.05) of prominent markers of angiogenesis, such as vonWillebrand factor (vWF) (∼ 2.5-fold) and CD31 (∼ 2-fold) in HUVECs stimulated with conditioned media from the androgen-independent prostate cancer cell line PC3. By mining the proteome of PC3 conditioned media, we discovered a signature of chemokine CXC motif ligands (i.e., CXCL3, CXCL5, CXCL6 and CXCL8) that could potentially coordinate increased angiogenesis in androgen-independent prostate cancer and verified their increased expression (P < 0.05) in both in vitro and xenograft models of androgen-independence. Our findings form the basis for understanding the regulation of crucial metastatic phenomena during the transition of androgen-dependent prostate cancer into the highly aggressive, androgen-independent state and provide further insight on potential therapeutic targets of cancer-related angiogenesis.