Int. J. Mol. Sci. 2013, 14(5), 10483-10496; doi:10.3390/ijms140510483
Article

Inhibition of CCL2 Signaling in Combination with Docetaxel Treatment Has Profound Inhibitory Effects on Prostate Cancer Growth in Bone

1 Department of Urology, University of Washington, Seattle, WA 98195, USA 2 Department of Orthopedic Surgery, Wayne State University, Detroit, MI 48202, USA 3 Janssen Research and Development, LLC, Spring House, PA 19002, USA
* Author to whom correspondence should be addressed.
Received: 16 February 2013; in revised form: 14 March 2013 / Accepted: 6 May 2013 / Published: 21 May 2013
(This article belongs to the Special Issue Molecular Research in Urology)
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Abstract: The C-C chemokine ligand 2 (CCL2) stimulates migration, proliferation, and invasion of prostate cancer (PCa) cells, and its signaling also plays a role in the activation of osteoclasts. Therefore targeting CCL2 signaling in regulation of tumor progression in bone metastases is an area of intense research. The objective of our study was to investigate the efficacy of CCL2 blockade by neutralizing antibodies to inhibit the growth of PCa in bone. We used a preclinical model of cancer growth in the bone in which PCa C4-2B cells were injected directly into murine tibiae. Animals were treated for ten weeks with neutralizing anti-CCL2 antibodies, docetaxel, or a combination of both, and then followed an additional nine weeks. CCL2 blockade inhibited the growth of PCa in bone, with even more pronounced inhibition in combination with docetaxel. CCL2 blockade also resulted in increases in bone mineral density. Furthermore, our results showed that the tumor inhibition lasted even after discontinuation of the treatment. Our data provide compelling evidence that CCL2 blockade slows PCa growth in bone, both alone and in combination with docetaxel. These results support the continued investigations of CCL2 blockade as a treatment for advanced metastatic PCa.
Keywords: prostate cancer; bone metastases; chemokine; CCL2; docetaxel; bone metastases

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MDPI and ACS Style

Kirk, P.S.; Koreckij, T.; Nguyen, H.M.; Brown, L.G.; Snyder, L.A.; Vessella, R.L.; Corey, E. Inhibition of CCL2 Signaling in Combination with Docetaxel Treatment Has Profound Inhibitory Effects on Prostate Cancer Growth in Bone. Int. J. Mol. Sci. 2013, 14, 10483-10496.

AMA Style

Kirk PS, Koreckij T, Nguyen HM, Brown LG, Snyder LA, Vessella RL, Corey E. Inhibition of CCL2 Signaling in Combination with Docetaxel Treatment Has Profound Inhibitory Effects on Prostate Cancer Growth in Bone. International Journal of Molecular Sciences. 2013; 14(5):10483-10496.

Chicago/Turabian Style

Kirk, Peter S.; Koreckij, Theodore; Nguyen, Holly M.; Brown, Lisha G.; Snyder, Linda A.; Vessella, Robert L.; Corey, Eva. 2013. "Inhibition of CCL2 Signaling in Combination with Docetaxel Treatment Has Profound Inhibitory Effects on Prostate Cancer Growth in Bone." Int. J. Mol. Sci. 14, no. 5: 10483-10496.

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