Serum caveolin-1, a biomarker of drug response and therapeutic target in prostate cancer models

Salahaldin A. Tahir, Shinji Kurosaka, Ryuta Tanimoto, Alexei A. Goltsov, Sanghee Park, Timothy C. Thompson

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

We investigated the effect of dasatinib and sunitinib on tyrosine kinase (TK) signaling, caveolin-1 (Cav-1) expression and secretion and proliferation of PC-3 and DU145 prostate cancer cells in vitro and in vivo. Treatment of both cell lines with either dasatinib or sunitinib reduced phosphorylation of PDGFR, VEGFR2, Akt, FAK, Src (dasatinib only) and Cav-1, and reduced cellular and secreted levels of Cav-1. Both agents dose-dependently inhibited proliferation of these cells. In PC-3 and DU145 subcutaneous xenografts, treatment with dasatinib, sunitinib or anti-Cav-1 antibody (Ab) alone produced significant tumor regression compared with that by vehicle or IgG alone. Combined dasatinib and anti-Cav-1 Ab treatment or sunitinib and anti-Cav-1 Ab produced greater tumor regression than either treatment alone. Serum Cav-1 levels were lower in dasatinib- and sunitinib-treated mice than they were in vehicle-treated mice, and correlated positively with tumor growth in dasatinib- and sunitinib-treated groups (r = 0.48, p = 0.031; r = 0.554, p = 0.0065, respectively), compared with vehicle controls. Cav-1 knockdown, in combination with dasatinib or sunitinib treatment in PC-3 cells, caused a greater reduction in the phosphorylation of PDGFR-β and VEGFR2, and expression and secretion of PDGF-B and VEGF-A than that in PC-3 cells treated with dasatinib or sunitinib alone in control siRNA cells, suggesting that Cav-1 is involved in an autocrine pathway that is affected by these drugs. Overall, our results suggest a role for Cav-1 as a biomarker of response to both dasatinib and sunitinib treatment and as a therapeutic target in prostate cancer.

Original languageEnglish
Pages (from-to)117-126
Number of pages10
JournalCancer Biology and Therapy
Volume14
Issue number2
DOIs
Publication statusPublished - Feb 2013

Keywords

  • Biomarkers
  • Caveolin-1
  • Prostate cancer
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Fingerprint Dive into the research topics of 'Serum caveolin-1, a biomarker of drug response and therapeutic target in prostate cancer models'. Together they form a unique fingerprint.

  • Cite this

    Tahir, S. A., Kurosaka, S., Tanimoto, R., Goltsov, A. A., Park, S., & Thompson, T. C. (2013). Serum caveolin-1, a biomarker of drug response and therapeutic target in prostate cancer models. Cancer Biology and Therapy, 14(2), 117-126. https://doi.org/10.4161/cbt.22633