Proteomic signatures of angiogenesis in androgen-independent prostate cancer

George S. Karagiannis, Punit Saraon, Keith A. Jarvi, Eleftherios P. Diamandis

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Introduction 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. METHODS 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. RESULTS 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. DISCUSSION 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. Prostate 74:260-272, 2014.

Original languageEnglish (US)
Pages (from-to)260-272
Number of pages13
JournalProstate
Volume74
Issue number3
DOIs
StatePublished - Feb 2014
Externally publishedYes

Keywords

  • androgen-independent cancer
  • chemokines
  • mass spectrometry
  • prostate cancer angiogenesis
  • prostate cancer proteomics

ASJC Scopus subject areas

  • Oncology
  • Urology

Fingerprint Dive into the research topics of 'Proteomic signatures of angiogenesis in androgen-independent prostate cancer'. Together they form a unique fingerprint.

Cite this