Bcl-2 mediated modulation of vascularizationin prostate cancer xenografts

Yoshihisa Sakai, Steve Goodison, Sergei Kusmartsev, Bradley Fletcher, Evgeniy Eruslanov, Wengang Cao, Stacy Porvasnik, Kazunori Namiki, Satoshi Anai, Charles J. Rosser

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

PURPOSE. We previously demonstrated that Bcl-2 overexpression enhances the radiation resistance of PC-3 human prostate cancer cells and xenografts by inhibiting apoptosis, increasing proliferation, and promoting angiogenesis. To further elucidate the relationship between Bcl-2 expression and the angiogenic potential of PC-3-Bcl-2 cells, tumorigenicity, angiogenesis, and lymphangiogenesis were evaluated and compared in a Bcl-2 overexpressing clone in vitro and in vivo. EXPERIMENTAL DESIGN. Human prostate cancer cells over expressing Bcl-2 were studied in vitro and in vivo to determine the angiogenic and lymphangiogenic properties of these cells. RESULTS. Increased Bcl-2 expression enhanced the tumorigenicity of prostate cancer xenografts. It also enhanced the expression and secretion of key angiogenic and lymphangiogenic factors that stimulated the synthesis of CD31-positive blood vessels and LYVE-1 positive lymphatics. Specifically, the increased angiogenic and lymphangiogenic potential correlated with increased serum levels of basic fibroblast growth factor (bFGF), interleukin 8 (CXCL8), and matrix metalloproteinase (MMP 9). In vitro analysis demonstrated that Bcl-2 expressing tumor cells secreted bFGF and vascular endothelial growth factor (VEGF) into culture supernatants. Microarray analysis of Bcl-2 expressing PC-3 cells demonstrated increased transcription of genes involved in metabolism, such as interleukins, growth factors, tumor necrosis factors (TNF) family members, and peptidases. CONCLUSIONS. Together, these results demonstrate that Bcl-2 can regulate tumoral angiogenesis and lymphangiogenesis and suggest that therapy targeted at Bcl-2 expression, angiogenesis, and lymphangiogenesis may synergistically modulate tumor growth and confirm that Bcl-2 is a pivotal target for cancer therapy.

Original languageEnglish (US)
Pages (from-to)459-470
Number of pages12
JournalProstate
Volume69
Issue number5
DOIs
StatePublished - Apr 1 2009

Keywords

  • Angiogenesis
  • Basic fibroblast growth factor
  • Bcl-2
  • Lymphangiogenesis
  • Microenvironment
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Oncology
  • Urology

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    Sakai, Y., Goodison, S., Kusmartsev, S., Fletcher, B., Eruslanov, E., Cao, W., Porvasnik, S., Namiki, K., Anai, S., & Rosser, C. J. (2009). Bcl-2 mediated modulation of vascularizationin prostate cancer xenografts. Prostate, 69(5), 459-470. https://doi.org/10.1002/pros.20888