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Cross-talk of Ito(stellate) cell and preneoplastic and cancer cells of hepatocarcinogenesis

伊藤星状细胞与肝癌癌前及癌细胞的串扰

基本信息

批准号：
11670507
负责人：
SAKAIDA Isao
金额：
$ 2.11万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670507/
关键词：
Stellate cell Cancer cell preneoplastic lesion fibrosis TGF-beta 1 伊藤細胞癌伊東細胞 TGF-β シグナル伝達

项目摘要

Our finding during investigation terms are as follows ;(1) Choline deficient L-amino acid (CDAA) defined diet induced hepatocyte cell death and regeneration resulting in stellate cell activation leading to preneoplastic lesions surrounded with fibrosis. Treatment with anti-fibrotic agent e.g. prolyl 4-hydrohylase inhibitor lead to the inhibition of stellate cell activation resulting in the prevention of preneoplastic lesions with reduced fibrosis without the protection of cell death.(2) Treatment rats with Choline deficient L-amino acid (CDAA) defined diet induced the cell death and regeneration causing the activation of Kupffer and stellate cells which will produce TGF-beta 1 resulting in the perpetuation of fibrosis.(3) Addition of the supernatant of cultured hepatic cancer cells on stellate cells induced activation of MAP kinase pathway but addition of the supernatant of stellate cells on cancer cells did not change the cell cycle of cancer cell. Co-culture of stellate cells and cancer cells indicated that the movement of stellate cells to cancer cells. This result may suggest the prevention of cancer cell invasion by stellate cells. However further studies are necessary.(4) The activation of MAP kinase pathway by using adenovirus system revealed that the expression of MMP-9 is regulated mainly by ERK pathway and MMP-13 is regulated by P38 pathway independently.These results will give the new insight for the therapy of liver fibrosis as well as the mechanism of cancer metastasis.

我们在研究期间的发现如下：(1)胆碱缺乏的L氨基酸限定饮食诱导肝细胞死亡和再生，导致星状细胞激活，导致癌前病变伴纤维化。(2)胆碱缺乏L氨基酸限定饮食处理大鼠可诱导细胞死亡和再生，引起Kupffer细胞和星状细胞的激活，从而产生转化生长因子-β1，从而使纤维化持续存在。(3)将培养的肝癌细胞上清液添加到星状细胞上可诱导MAP激酶途径的激活，但加入癌细胞上的星状细胞上清液并不改变癌细胞的细胞周期。星状细胞与癌细胞共培养表明星状细胞向癌细胞运动。这一结果可能提示星状细胞可以预防癌细胞的侵袭。腺病毒系统激活MAP激酶通路表明，MMP9的表达主要受ERK途径的调控，而MMP13的表达独立受P38途径的调控，这一结果将为肝纤维化的治疗以及肿瘤转移机制的研究提供新的思路。