Synergy between anti-CCL2 and docetaxel as determined by DW-MRI in a metastatic bone cancer model

Stefan Rozel, Craig J. Galbán, Klaas Nicolay, Kuei C. Lee, Sudha Sud, Chris Neeley, Linda A. Snyder, Thomas L. Chenevert, Alnawaz Rehemtulla, Brian D. Ross, Kenneth Pienta

Research output: Contribution to journalArticle

Abstract

Metastatic prostate cancer continues to be the second leading cause of cancer death in American men with an estimated 28,660 deaths in 2008. Recently, monocyte chemoattractant protein-1 (MCP-1, CCL2) has been identified as an important factor in the regulation of prostate metastasis. CCL2, shown to attract macrophages to the tumor site, has a direct promotional effect on tumor cell proliferation, migration, and survival. Previous studies have shown that anti-CCL2 antibodies given in combination with docetaxel were able to induce tumor regression in a pre-clinical prostate cancer model. A limitation for evaluating new treatments for metastatic prostate cancer to bone is the inability of imaging to objectively assess response to treatment. Diffusion-weighted MRI (DW-MRI) assesses response to anticancer therapies by quantifying the random (i.e., Brownian) motion of water molecules within the tumor mass, thus identifying cells undergoing apoptosis. We sought to measure the treatment response of prostate cancer in an osseous site to docetaxel, an anti-CCL2 agent, and combination treatments using DW-MRI. Measurements of tumor apparent diffusion coefficient (ADC) values were accomplished over time during a 14-day treatment period and compared to response as measured by bioluminescence imaging and survival studies. The diffusion data provided early predictive evidence of the most effective therapy, with survival data results correlating with the DW-MRI findings. DW-MRI is under active investigation in the pre-clinical and clinical settings to provide a sensitive and quantifiable means for early assessment of cancer treatment outcome.

Original languageEnglish (US)
Pages (from-to)58-64
Number of pages7
JournalJournal of Cellular Biochemistry
Volume107
Issue number1
DOIs
StatePublished - May 1 2009
Externally publishedYes

Fingerprint

docetaxel
Bone Neoplasms
Diffusion Magnetic Resonance Imaging
Magnetic resonance imaging
Bone
Tumors
Prostatic Neoplasms
Neoplasms
Therapeutics
Bioluminescence
Imaging techniques
Oncology
Chemokine CCL2
Macrophages
Brownian movement
Cell proliferation
Survival
Cell Movement
Prostate
Cause of Death

Keywords

  • Chemotherapy
  • Macrophages
  • Prostate cancer

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Synergy between anti-CCL2 and docetaxel as determined by DW-MRI in a metastatic bone cancer model. / Rozel, Stefan; Galbán, Craig J.; Nicolay, Klaas; Lee, Kuei C.; Sud, Sudha; Neeley, Chris; Snyder, Linda A.; Chenevert, Thomas L.; Rehemtulla, Alnawaz; Ross, Brian D.; Pienta, Kenneth.

In: Journal of Cellular Biochemistry, Vol. 107, No. 1, 01.05.2009, p. 58-64.

Research output: Contribution to journalArticle

Rozel, S, Galbán, CJ, Nicolay, K, Lee, KC, Sud, S, Neeley, C, Snyder, LA, Chenevert, TL, Rehemtulla, A, Ross, BD & Pienta, K 2009, 'Synergy between anti-CCL2 and docetaxel as determined by DW-MRI in a metastatic bone cancer model', Journal of Cellular Biochemistry, vol. 107, no. 1, pp. 58-64. https://doi.org/10.1002/jcb.22056
Rozel, Stefan ; Galbán, Craig J. ; Nicolay, Klaas ; Lee, Kuei C. ; Sud, Sudha ; Neeley, Chris ; Snyder, Linda A. ; Chenevert, Thomas L. ; Rehemtulla, Alnawaz ; Ross, Brian D. ; Pienta, Kenneth. / Synergy between anti-CCL2 and docetaxel as determined by DW-MRI in a metastatic bone cancer model. In: Journal of Cellular Biochemistry. 2009 ; Vol. 107, No. 1. pp. 58-64.
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