Attenuated liver tumor formation in the absence of CCR2 with a concomitant reduction in the accumulation of hepatic stellate cells, macrophages and neovascularization

フォーマット:

論文

責任表示:

Yang, Xiaoqin ; Lu, Peirong ; Ishida, Yuko ; Kuziel, William A. ; Fujii, Chifumi ; Mukaida, Naofumi

言語:

英語

出版情報:

Wiley-Liss, 2006-11-15

著者名:

Yang, Xiaoqin

Lu, Peirong

Ishida, Yuko

Kuziel, William A.

Fujii, Chifumi

Mukaida, Naofumi

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掲載情報:

International Journal of Cancer

ISSN:

1097-0215      

巻:

118

通号:

2

開始ページ:

335

終了ページ:

345

バージョン:

author

概要:

金沢大学がん研究所がん病態制御<br />The liver parenchyma is populated by hepatocytes and several nonparenchymal cell types, including Kupffer cells and hepatic stellate cells. Both Kupffer cells and hepatic stellate cells are responsive to the chemo … kine CCL2, but the precise roles of CCL2 and these cells in liver tumor formation remain undefined. Hence, we investigated the effects of the lack of the major CCL2 receptor, CCR2, on liver tumor formation induced by intraportal injection of the murine colon adenocarcinoma cell line, colon 26. Wild-type mice showed macroscopic tumor foci in the liver 10 days after injection of colon 26 cells. After 10 days, CCL2 proteins were detected predominantly in tumor cells, coincident with increased intratumoral macrophage and hepatic stellate cell numbers. Although tumor formation occurred at similar rates in wild-type and CCR2-deficient mice up to 10 days after tumor cell injection, the number and size of tumor foci were significantly attenuated in CCR2-deficient mice relative to wild-type mice thereafter. Moreover, neovascularization and matrix metalloproteinase 2 expression were diminished in CCR2-deficient mice with a concomitant reduction in the accumulation of macrophages and hepatic stellate cells. Furthermore, matrix metalloproteinase 2 was detected predominantly in hepatic stellate cells but not in macrophages. We provided the first definitive evidence that the absence of CCR2-mediated signals can reduce the trafficking of hepatic stellate cells, a main source of matrix metalloproteinase 2, and consequently can diminish neovascularization during liver tumor formation. © 2005 Wiley-Liss, Inc. 続きを見る

URL:

http://hdl.handle.net/2297/6665