Blockade of a chemokine, CCL2, reduces chronic colitis-associated carcinogenesis in mice

• Popivanova, Boryana Konstantinova

• Kostadinova, Feodora Ivanova

• Furuichi, Kengo

• Shamekh, Mohamed M.

• Kondo, Toshikazu

• Wada, Takashi

• Egashira, Kensuke

• Mukaida, Naofumi

抄録

金沢大学がん研究所がん病態制御

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. ©2009 American Association for Cancer Research.

収録刊行物

• Cancer Research

  Cancer Research 69 (19), 7884-7892, 2009-10-01

  American Association for Cancer Research

詳細情報

• CRID: 1050564285937514368
• NII論文ID: 120001728440
• NII書誌ID: AA00598557
• ISSN: 00085472
• Web Site: http://hdl.handle.net/2297/19814
• 本文言語コード: en
• 資料種別: journal article
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