Effects of CXCR4 antagonist CTCE-9908 on prostate tumor growth

Stacy Porvasnik, Noboru Sakamoto, Sergei Kusmartsev, Evgeniy Eruslanov, Wan Ju Kim, Wengang Cao, Cydney Urbanek, Donald Wong, Steve Goodison, Charles J. Rosser

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

BACKGROUND. Recent reports have linked the survival-promoting effect of CXCR4 to the up regulation of Bcl-2 protein expression. MATERIALS AND METHODS. To further elucidate the relationship between Bcl-2 and CXCR4, tumorigenicity was evaluated in in vitro and in vivo models following treatment with CTCE-9908, a CXCR4 antagonist peptide. RESULTS. In vitro, CTCE-9908 inhibited cellular proliferation in PC-3-Bcl-2 and PC-3-Neo cell lines Furthermore in our xenograft model, CTCE-9908 delivered via daily intraperitoneal injections resulted in a statistically significant reduction in tumor size compared to control (396 + 205 mm3 vs. 1,010 + 215 mm3 respectively, p < 0.05) in the Bcl-2 expressing tumors. This reduction was associated with knockdown of VEGF, inhibition of angiogenesis and lymphangiogenesis, and induction of apoptosis. CTCE-9908 therapy was also associated with a marked reduction in intra-tumoral host cells expressing VEGFR1 and CD11b myeloid-derived suppressor cells (MDSC). CONCLUSION. These data show that CXCR4 antagonists represent a valuable addition to the cancer therapeutic arsenal. Such agents may have beneficial synergistic dual-effects in reducing tumor cell proliferation directly, and indirectly through perturbation of the tumor microenvironment. Further studies of the novel CTCE-9908 compound in prostate and other solid tumor inhibition are warranted.

Original languageEnglish (US)
Pages (from-to)1460-1469
Number of pages10
JournalProstate
Volume69
Issue number13
DOIs
StatePublished - Sep 15 2009

Keywords

  • Apoptotic
  • Bcl-2
  • CTCE-9908
  • CXCR4
  • Therapeutic

ASJC Scopus subject areas

  • Oncology
  • Urology

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    Porvasnik, S., Sakamoto, N., Kusmartsev, S., Eruslanov, E., Kim, W. J., Cao, W., Urbanek, C., Wong, D., Goodison, S., & Rosser, C. J. (2009). Effects of CXCR4 antagonist CTCE-9908 on prostate tumor growth. Prostate, 69(13), 1460-1469. https://doi.org/10.1002/pros.21008