Blockade of the chemokine receptor, CCR5, reduces the growth of orthotopically injected colon cancer cells via limiting cancer-associated fibroblast accumulation.

Abstract

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.

• Authors: Yamato Tanabe, Soichiro Sasaki, Naofumi Mukaida, Tomohisa Baba
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 30 Pg. 48335-48345 (07 26 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27340784 (Publication Type: Journal Article)

Chemical References

• CCR5 Receptor Antagonists
• CCR5 protein, human
• CCR5 protein, mouse
• Cyclohexanes
• Receptors, CCR5
• Triazoles
• Maraviroc

Topics

• Animals
• CCR5 Receptor Antagonists (pharmacology)
• Cell Line, Tumor
• Colonic Neoplasms (drug therapy, metabolism, pathology)
• Cyclohexanes (pharmacology)
• Female
• Fibroblasts (drug effects, metabolism, pathology)
• Humans
• Male
• Maraviroc
• Mice
• Mice, Inbred BALB C
• NIH 3T3 Cells
• Receptors, CCR5 (metabolism)
• Triazoles (pharmacology)