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.

我们在调查期间的发现如下：（1）胆碱缺乏L-氨基酸（CDAA）定义的饮食诱导肝细胞死亡和再生，导致星状细胞活化，导致周围纤维化的癌前病变。使用抗纤维化药物治疗，例如脯氨酰 4-水解酶抑制剂可抑制星状细胞活化，从而预防癌前病变，同时减少纤维化，但不保护细胞死亡。(2) 用胆碱缺乏 L-氨基酸 (CDAA) 限定饮食治疗大鼠，诱导细胞死亡死亡和再生引起枯否细胞和星状细胞的激活，从而产生 TGF-β1，导致纤维化永久化。(3) 添加在星状细胞上培养的肝癌细胞诱导MAP激酶途径的激活，但在癌细胞上添加星状细胞上清液并没有改变癌细胞的细胞周期。星状细胞和癌细胞的共培养表明星状细胞向癌细胞的运动。这一结果可能表明星状细胞可以预防癌细胞的侵袭。 (4)腺病毒系统对MAP激酶通路的激活表明MMP-9的表达主要受ERK通路调控,MMP-13的表达主要受P38通路独立调控。这些结果将为新的研究提供新的思路。对肝纤维化治疗以及癌症转移机制的见解。