Stacy Porvasnik and Noboru Sakamoto contributed equally to this work.
Effects of CXCR4 antagonist CTCE-9908 on prostate tumor growth†
Article first published online: 8 JUL 2009
Copyright © 2009 Wiley-Liss, Inc.
Volume 69, Issue 13, pages 1460–1469, 15 September 2009
How to Cite
Porvasnik, S., Sakamoto, N., Kusmartsev, S., Eruslanov, E., Kim, W.-J., Cao, W., Urbanek, C., Wong, D., Goodison, S. and Rosser, C. J. (2009), Effects of CXCR4 antagonist CTCE-9908 on prostate tumor growth. Prostate, 69: 1460–1469. doi: 10.1002/pros.21008
- Issue published online: 20 AUG 2009
- Article first published online: 8 JUL 2009
- Manuscript Accepted: 5 JUN 2009
- Manuscript Received: 16 APR 2009
- Flight Attendant Medical Research Institute
- American Cancer Society Research Scholar Award. Grant Number: RSG-06-265-01-MBC
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.
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).
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. Prostate 69: 1460–1469, 2009. © 2009 Wiley-Liss, Inc.