Hepatocyte Growth Factor Inhibits Anoikis of Pancreatic Carcinoma Cells Through Phosphatidylinositol 3-Kinase Pathway
Hepatocyte Growth Factor Inhibits Anoikis of Pancreatic Carcinoma Cells Through Phosphatidylinositol 3-Kinase Pathway
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DOI：
10.1097/mpa.0b013e318214fa6c
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发表时间：
2011-05-01
期刊：
影响因子：
2.9
通讯作者：
Yokosuka, Osamu
中科院分区：
文献类型：
--
作者：
Watanabe, Satoshi;Kishimoto, Takashi;Yokosuka, Osamu
目的：失巢凋亡是指细胞与细胞或细胞与细胞外基质相互作用的丧失所导致的细胞凋亡，其逃逸在肿瘤的侵袭和转移中起重要作用。肝细胞生长因子（HGF）在胰腺癌中起着重要作用。本研究旨在探讨肝细胞生长因子（HGF）对胰腺癌细胞的抗失巢凋亡作用。Western blot分析和磷脂酰肌醇3-激酶（PI 3 K）和p38抑制剂对信号通路的抑制作用。然而，一些癌细胞通过在悬浮液中形成聚集体而存活。抗E-钙粘蛋白抗体使聚集体解离，并且分离的细胞经历额外的失巢凋亡。肝细胞生长因子抑制失巢凋亡无关E-钙粘蛋白介导的细胞-细胞接触。抑制磷脂酰肌醇3-激酶/Akt通路可消除HGF的抗失巢凋亡作用。结论：肝细胞生长因子通过激活Akt激活的磷脂酰肌醇3-激酶途径抑制胰腺癌细胞的失巢凋亡。因此，HGF可能通过发挥其抗失巢凋亡作用，在胰腺癌细胞的侵袭和转移中发挥重要作用。
Objectives: Escape from anoikis, apoptosis induced by loss of cell-cell or cell-extracellular matrix interactions, is important in tumor invasion and metastasis. Hepatocyte growth factor (HGF) is known to play a pivotal role in pancreatic carcinomas. This study aimed to determine the antianoikis effect of HGF in pancreatic carcinoma cells.Methods: Antianoikis effect of HGF was evaluated in human pancreatic carcinoma cells in nonadherent culture with or without anti-E-cadherin antibody. Signal pathways were investigated by Western blot analysis and inhibition assay using inhibitors for phosphatidylinositol 3-kinase and p38.Results: Pancreatic carcinoma cells underwent anoikis in nonadherent culture. However, some of the carcinoma cells survived by forming aggregations in suspension. Anti-E-cadherin antibody dissociated the aggregations, and the separated cells underwent additional anoikis. Hepatocyte growth factor inhibited anoikis irrespective of E-cadherin-mediated cell-cell contact. Inhibition of the phosphatidylinositol 3-kinase/Akt pathway abolished the antianoikis effect of HGF. Phosphorylation of Akt was induced by HGF, and the phosphorylated Akt persisted even when E-cadherin was inhibited.Conclusions: Hepatocyte growth factor inhibits anoikis of pancreatic carcinoma cells through phosphatidylinositol 3-kinase pathway in which activation of Akt may be involved. It is thus supposed that HGF may have a potent role in invasion and metastasis of pancreatic carcinoma cells by exerting its antianoikis effect.