FGF10/FGFR2 signal induces cell migration and invasion in pancreatic cancer.
FGF10/FGFR2 signal induces cell migration and invasion in pancreatic cancer.
复制标题
FGF10/FGFR2信号诱导胰腺癌细胞迁移和侵袭。
DOI：
10.1038/sj.bjc.6604473
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发表时间：
2008-07-22
影响因子：
8.8
通讯作者：
Miyazaki, M.
中科院分区：
文献类型：
--
作者：
Nomura, S.;Yoshitomi, H.;Takano, S.;Shida, T.;Kobayashi, S.;Ohtsuka, M.;Kimura, F.;Shimizu, H.;Yoshidome, H.;Kato, A.;Miyazaki, M.
关键词：
胰腺癌是所有恶性肿瘤中死亡率最高的癌症之一，迫切需要新的治疗方法。这可能通过解决详细的生物学机制来实现，在这项研究中，我们通过关注成纤维细胞生长因子 (FGF)10 和 FGF 受体 (FGFR)2 的信号传导来研究胰腺癌细胞如何产生侵袭性，这两种因子在胰腺器官发生中发挥着重要作用。胰腺癌组织的免疫染色显示，FGFR2在癌细胞中表达，而FGF10在癌细胞周围的基质细胞中表达。癌细胞中FGFR2高表达的患者比FGFR2低表达的患者生存时间更短。成纤维细胞生长因子 10 通过与 FGFR2-IIIb（FGFR2 的一种特定亚型）相互作用，诱导 CFPAC-1 和 AsPC-1 胰腺癌细胞的细胞迁移和侵袭。成纤维细胞生长因子 10 还诱导膜 1 型基质金属蛋白酶 (MT1-MMP) 和转化生长因子 (TGF)-β1 的 mRNA 表达，并增加这些细胞系 TGF-β1 蛋白的分泌。这些数据表明基质 FGF10 通过与 FGFR2 相互作用诱导胰腺癌细胞迁移和侵袭，导致预后不良。这表明 FGF10/FGFR2 信号传导是针对胰腺癌的新分子疗法的一个有希望的靶点。
Pancreatic cancer has one of the highest mortalities among all malignancies and there is an urgent need for new therapy. This might be achieved by resolving the detailed biological mechanism, and in this study we examined how pancreatic cancer cells develop aggressive properties by focusing on signalling through the fibroblast growth factor (FGF)10 and FGF receptor (FGFR)2, which play important roles in pancreatic organogenesis. Immunostaining of pancreatic cancer tissues showed that FGFR2 was expressed in cancer cells, whereas FGF10 was expressed in stromal cells surrounding the cancer cells. Patients with high FGFR2 expression in cancer cells had a shorter survival time compared to those with low FGFR2 expression. Fibroblast growth factor 10 induced cell migration and invasion of CFPAC-1 and AsPC-1 pancreatic cancer cells through interaction with FGFR2-IIIb, a specific isoform of FGFR2. Fibroblast growth factor 10 also induced expression of mRNA for membrane type 1-matrix metalloproteinase (MT1-MMP) and transforming growth factor (TGF)-β1, and increased secretion of TGF-β1 protein from these cell lines. These data indicate that stromal FGF10 induces migration and invasion in pancreatic cancer cells through interaction with FGFR2, resulting in a poor prognosis. This suggests that FGF10/FGFR2 signalling is a promising target for new molecular therapy against pancreatic cancer.
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