| First Author | Sasaki S | Year | 2014 |
| Journal | Int J Cancer | Volume | 135 |
| Issue | 6 | Pages | 1297-306 |
| PubMed ID | 24510316 | Mgi Jnum | J:214347 |
| Mgi Id | MGI:5588789 | Doi | 10.1002/ijc.28779 |
| Citation | Sasaki S, et al. (2014) Crucial involvement of the CCL3-CCR5 axis-mediated fibroblast accumulation in colitis-associated carcinogenesis in mice. Int J Cancer 135(6):1297-306 |
| abstractText | Patients with inflammatory bowel diseases often develop colon carcinoma. Combined treatment of azoxymethane (AOM) and dextran sulfate sodium (DSS) recapitulates colitis-associated cancer in mice. AOM/DSS-induced tumor formation was reduced in CCL3- or its specific receptor, CCR5-deficient mice despite the presence of a massive infiltration of inflammatory cells. However, AOM/DSS-induced type I collagen-positive fibroblast accumulation in the colon was reduced in CCL3- or CCR5-deficient mice. This was associated with depressed expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF), which is expressed mainly by fibroblasts. Moreover in vitro, CCL3 induced fibroblasts to proliferate and to enhance HB-EGF expression. Furthermore, CCR5 blockade reduced tumor formation together with reduced fibroblast accumulation and HB-EGF expression, even when administered after the development of multiple colon tumors. Thus, CCL3-CCR5-mediated fibroblast accumulation may be required, in addition to leukocyte infiltration, to induce full-blown colitis-associated carcinogenesis. Our studies shed light on a therapeutic potential of CCR5 antagonist for patients with colitis-associated cancer. |
