Blockade of a Chemokine, CCL2, Reduces Chronic Colitis-Associated Carcinogenesis in Mice
| Autor: | Boryana K. Popivanova, Feodora I. Kostadinova, Kengo Furuichi, Naofumi Mukaida, Takashi Wada, Mohamed M. Shamekh, Toshikazu Kondo, Kensuke Egashira |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Cancer Research CCR2 Chemokine Receptors CCR2 Azoxymethane Mice Transgenic Inflammation medicine.disease_cause Intracolonic Mice chemistry.chemical_compound Organometallic Compounds Animals Humans Medicine RNA Messenger Colitis Chemokine CCL2 Mice Inbred BALB C biology Germanium business.industry Dextran Sulfate medicine.disease Ulcerative colitis digestive system diseases Oncology chemistry Cyclooxygenase 2 Colonic Neoplasms Immunology biology.protein Colitis Ulcerative Female Propionates medicine.symptom business Carcinogenesis |
| Zdroj: | Cancer Research. 69:7884-7892 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-09-1451 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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