Blockade of the chemokine receptor, CCR5, reduces the growth of orthotopically injected colon cancer cells via limiting cancer-associated fibroblast accumulation
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Yamato Tanabe1, Soichiro Sasaki1, Naofumi Mukaida1, Tomohisa Baba1
1Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
Tomohisa Baba, email: [email protected]
Keywords: colorectal cancer, CCL3, CCR5, cancer-associated fibroblast, maraviroc
Received: January 26, 2016 Accepted: June 07, 2016 Published: June 22, 2016
We previously demonstrated that cancer-associated fibroblasts (CAFs) accumulate at tumor sites through the interaction between a chemokine, CCL3, and its receptor, CCR5, in the late phase of colitis-associated colon carcinogenesis. Here we examined the effect of a CCR5 antagonist, maraviroc, on tumor growth arising from the orthotopic injection of mouse or human colon cancer cell lines into the cecal wall by focusing on CAFs. Orthotopic injection of either cell line caused tumor formation together with leukocyte infiltration and fibroblast accumulation. Concomitant oral administration of maraviroc reduced tumor formation with few effects on leukocyte infiltration. In contrast, maraviroc reduced the intratumor number of α-smooth muscle actin-positive fibroblasts, which express epidermal growth factor, a crucial growth factor for colon cancer cell growth. These observations suggest that maraviroc or other CCR5 antagonists might act as novel anti-CRC drugs to dampen CAFs, an essential cell component for tumor progression.
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