Document Type

Article

Abstract

Abstract

Background

CXCL12/CXCR4 transactivation of epidermal growth factor family receptors in lipid raft membrane microdomains on cell surface is thought to mediate tumor growth and subsequent development of metastatic disease. CTCE-9908 is a known inhibitor of CXCR4. Herein, we tested the efficacy of CTCE-9908 in inhibiting prostate cancer cell growth, invasion, and metastasis.

Methods

We used a panel ofin vitroassays utilizing human prostate cancer cell lines and anin vivoorthotopic prostate cancer model to assess the anti-tumoral activity of CTCE-9908.

Results

We demonstrated that (a) CTCE-9908 treatment resulted in no significant change in the growth of PC-3 and C4-2B cells; (b) 50 μg/ml of CTCE-9908 inhibited the invasive properties of PC-3 cells; (c) 25 mg/kg of CTCE-9908 did not alter primary tumor growth but it did significantly reduce total tumor burden in the animal including the growth of prostate and soft tissue metastases to lymph node and distant organ tissues. Histological analysis showed that CTCE-9908 treatment resulted in tumor necrosis in primary prostate tumors and no significant change in proliferation of tumor cells as measured by Ki-67 staining; (d) CTCE-9908 inhibited the tumor angiogenesis as measured by CD34 positive vessels in tumors.

Conclusions

These data suggest that CXCR4 inhibition by CTCE-9908 decreases the invasion potentialin vitro, which then translated to a reduction of tumor spread with associated reduction in angiogenesis. Hence, CTCE-9908 may prove to be an efficacious novel agent to prevent and treat the spread of metastatic prostate cancer.

Disciplines

Cell and Developmental Biology | Microbiology

Acknowledgements

We would like to thank Dr. Charles J. Rosser (MD Anderson Cancer Center Orlando, Orlando, FL, USA) for critically reading and editing the manuscript to improve intellectual content. Supported by Fund for Cancer Research, U.S. Department of Defense, Idea Award W81XWH-09-1-0250 and NIH R01CA151557 to Sreenivasa R. Chinni.