American Association for Cancer Research
Browse
00085472can091451-sup-sfi_g4.pdf (4.76 MB)

Supplementary Figure 4 from Blockade of a Chemokine, CCL2, Reduces Chronic Colitis-Associated Carcinogenesis in Mice

Download (4.76 MB)
journal contribution
posted on 2023-03-30, 19:12 authored by Boryana Konstantinova Popivanova, Feodora Ivanova Kostadinova, Kengo Furuichi, Mohamed M. Shamekh, Toshikazu Kondo, Takashi Wada, Kensuke Egashira, Naofumi Mukaida
Supplementary Figure 4 from Blockade of a Chemokine, CCL2, Reduces Chronic Colitis-Associated Carcinogenesis in Mice

History

ARTICLE ABSTRACT

Accumulating evidence indicates the crucial contribution of chronic inflammation to various types of carcinogenesis, including colon carcinoma associated with ulcerative colitis and asbestosis-induced malignant mesothelioma. Ulcerative colitis–associated colon carcinogenesis can be recapitulated in mice by azoxymethane administration followed by repetitive dextran sulfate sodium ingestion. In the course of this carcinogenesis process, the expression of a macrophage-tropic chemokine, CCL2, was enhanced together with intracolonic massive infiltration of macrophages, which were a major source of cyclooxygenase (COX)-2, a crucial mediator of colon carcinogenesis. Mice deficient in CCL2-specific receptor, CCR2, exhibited less macrophage infiltration and lower tumor numbers with attenuated COX-2 expression. Moreover, CCL2 antagonists decreased intracolonic macrophage infiltration and COX-2 expression, attenuated neovascularization, and eventually reduced the numbers and size of colon tumors, even when given after multiple colon tumors have developed. These observations identify CCL2 as a crucial mediator of the initiation and progression of chronic colitis–associated colon carcinogenesis and suggest that targeting CCL2 may be useful in treating colon cancers, particularly those associated with chronic inflammation. [Cancer Res 2009;69(19):7884–92]