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, Steven Goodison, Charles J. Rosser

Research output: Contribution to journalArticle

81 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Prostate
Growth
Neoplasms
Cell Proliferation
Lymphangiogenesis
Tumor Microenvironment
Intraperitoneal Injections
Heterografts
Vascular Endothelial Growth Factor A
Up-Regulation
Therapeutics
CTCE-9908
Apoptosis
Cell Line
Peptides
Proteins
In Vitro Techniques

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Porvasnik, S., Sakamoto, N., Kusmartsev, S., Eruslanov, E., Kim, W. J., Cao, W., ... 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

Effects of CXCR4 antagonist CTCE-9908 on prostate tumor growth. / Porvasnik, Stacy; Sakamoto, Noboru; Kusmartsev, Sergei; Eruslanov, Evgeniy; Kim, Wan Ju; Cao, Wengang; Urbanek, Cydney; Wong, Donald; Goodison, Steven; Rosser, Charles J.

In: Prostate, Vol. 69, No. 13, 15.09.2009, p. 1460-1469.

Research output: Contribution to journalArticle

Porvasnik, S, Sakamoto, N, Kusmartsev, S, Eruslanov, E, Kim, WJ, Cao, W, Urbanek, C, Wong, D, Goodison, S & Rosser, CJ 2009, 'Effects of CXCR4 antagonist CTCE-9908 on prostate tumor growth', Prostate, vol. 69, no. 13, pp. 1460-1469. https://doi.org/10.1002/pros.21008
Porvasnik S, Sakamoto N, Kusmartsev S, Eruslanov E, Kim WJ, Cao W et al. Effects of CXCR4 antagonist CTCE-9908 on prostate tumor growth. Prostate. 2009 Sep 15;69(13):1460-1469. https://doi.org/10.1002/pros.21008
Porvasnik, Stacy ; Sakamoto, Noboru ; Kusmartsev, Sergei ; Eruslanov, Evgeniy ; Kim, Wan Ju ; Cao, Wengang ; Urbanek, Cydney ; Wong, Donald ; Goodison, Steven ; Rosser, Charles J. / Effects of CXCR4 antagonist CTCE-9908 on prostate tumor growth. In: Prostate. 2009 ; Vol. 69, No. 13. pp. 1460-1469.
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