Regulatory role of c-Met in insulin-like growth factor-I receptor-mediated migration and invasion of human pancreatic carcinoma cells
Regulatory role of c-Met in insulin-like growth factor-I receptor-mediated migration and invasion of human pancreatic carcinoma cells
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DOI：
10.1158/1535-7163.mct-05-0175
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发表时间：
2006-07-01
影响因子：
5.7
通讯作者：
Ellis, Lee M.
中科院分区：
文献类型：
--
作者：
Bauer, Todd W.;Somcio, Ray J.;Ellis, Lee M.
胰腺癌细胞过表达胰岛素样生长因子-I（IGF-I）受体（IGF-IR）和肝细胞生长因子（HGF）受体c-Met，这两种受体均已知介导肿瘤细胞迁移和侵袭。我们假设IGF-IR和c-Met协同诱导人胰腺癌细胞的迁移和侵袭，并且IGF-I介导的迁移和侵袭依赖于c-Met。用PBS、IGF-I、HGF或IGF-I加HGF处理的人胰腺癌细胞系L3.6pl进行迁移和侵袭测定。为了确定c-Met是否是IGF-IR介导的迁移和侵袭所必需的，在IGF-I处理之前，通过用c-Met核酶的腺病毒感染在L3.6pl细胞中下调c-Met。IGF-1和HGF增加细胞迁移和侵袭。此外，IGF-I加HGF对细胞迁移和侵袭的作用大于单独使用生长因子。下调c-Met几乎完全抑制IGF-I介导的迁移和侵袭。我们的研究结果表明，IGF-IR和c-Met协同诱导人胰腺癌细胞的迁移和侵袭。此外，c-Met是HGF和IGF-I介导的迁移和侵袭所必需的。阐明促进肿瘤进展和转移的信号通路将为胰腺癌靶向治疗的发展提供基础。
Pancreatic carcinoma cells overexpress the insulin-like growth factor-I (IGF-I) receptor (IGF-IR) and the hepatocyte growth factor (HGF) receptor, c-Met, which are both known to mediate tumor cell migration and invasion. We hypothesized that IGF-IR and c-Met cooperate to induce migration and invasion of human pancreatic carcinoma cells and that IGF-I-mediated migration and invasion depend on c-Met. Migration and invasion assays were done with the human pancreatic cancer cell line L3.6pl treated with PBS, IGF-I, HGF, or IGF-I plus HGF. To determine if c-Met is necessary for IGF-IR-mediated migration and invasion, c-Met was down-regulated in L3.6pl cells via adenoviral infection with a c-Met ribozyme before IGF-I treatment. lGF-I and HGF increased cell migration and invasion. Furthermore, IGF-I plus HGF had a greater than additive effect on cell migration and invasion compared with either growth factor alone. Down-regulation of c-Met nearly completely inhibited IGF-I-mediated migration and invasion. Our findings suggest that IGF-IR and c-Met cooperate to induce migration and invasion of human pancreatic carcinoma cells. Furthermore, c-Met is required for both HGF- and IGF-I-mediated migration and invasion. Elucidation of the signaling pathways that contribute to tumor progression and metastasis should provide a foundation for the development of targeted therapies for pancreatic carcinoma.