Role of Caveolin-1 in Prostate Cancer Angiogenesis

Abstract

We have proposed that prostate cancer cells secrete cav-1 which induces specific changes in EC which potentiate angiogenesis and metastatic activities. We have reported that prostate cancer cell derived, secreted caveolin-1 is taken up by cancer cells and tumor associated endothelial cells (Tahir et al, Cancer Res 2008). This autocrine/paracrine activity of secreted caveolin-1 promotes malignant progression by stimulation of specific angiogenic activities. We have shown in cav-1 negative LP-LNCaP cells that adenoviral vector mediated expression of cav-1 stimulated VEGF mediated VEGFR2 autophosphorylation and activated downstream signaling, whereas cav-1 knockdown in PC-3 and HUVECs impaired the VEGF-stimulated angiogenesis signaling. This showed cav-1 is an important regulator of basal and VEGF-stimulated angiogenesis signaling in prostate cancer cells and HUVECs (Tahir et al, Cancer Biol Ther 2009). Furthermore, we sought to determine whether there was any potential correlation between cav-1 and the GFs such as VEGF, TGF-beta1, and FGF2. Our work revealed that cav-1 enhances cancer cell motility in an Akt-dependent manner and it up-regulates VEGF, TGF-beta1 and FGF2 through Aktmediated maintenance of mRNA stability (Li et al. Mol Cancer Res 2009). Using cav-1 knock out mice system, we have shown wet prostate tumor weight of RM-9 was significantly reduced in cav-1-/- mice compared with cav-1+/+ mice. Also, tumor wet weight was significantly reduced in cav-1 / mice which received cav-1 Ab compared to the mice treated with control IgG or HBSS only. Treatment with cav-1 Ab produced reduced lung metastasis in cav-1-/- model and increased survival time compared to the cav-1-/- littermate treated with control IgG or HBSS only( Watanabe et al. Mol cancer Res. 2009).

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Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2009
Accession Number
ADA587089

Entities

People

  • Timothy C Thompson

Organizations

  • The University of Texas MD Anderson Cancer Center

Tags

DTIC Thesaurus Topics

  • Cancer
  • Carcinoma
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Health Services
  • Medical Personnel
  • Oncology
  • Peptide Growth Factors

Fields of Study

  • Biology

Readers

  • Aquatic Ecology
  • Breast cancer cell signaling and growth regulation.
  • Oncology (Cancer Research).