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Cancer stem cell analysis of pancreas duct cell carcinoma a fundamental study for new strategy against pancreatic cancer

胰腺导管细胞癌的癌症干细胞分析是抗胰腺癌新策略的基础研究

基本信息

批准号：
17591453
负责人：
ASANO Takehide
金额：
$ 2.24万
依托单位：
Chiba Cancer Center Research Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591453/
关键词：
Cancer Development Differentiation Cancer stem cell Metastasis Recurrence Pancreas pancreatic duct cell carcinoma

项目摘要

The stem cell nitch of pancreas and the role of cancer stem cells of pancreatic carcinogenesis has been elusive. We investigate the dedifferentiation ability of mouse derived pancreatic epithelial cells under stimulation of growth factors. We observed formation of cells with a mesenchymal phenotype in murine pancreatic explants cultured on gelatin-coated dishes in the presence of serum and/or growth factors; we refer to these cells as mAPCs (mouse acinar-derived pancreatic cells). On the first day of culture, most cells formed an acinar cell cluster with a high level of amylase. By day 3, a spheroid-like cell aggregate had formed and cells (mAPCs) with a fibroblast-like morphology that were positive for amylase and nestin began to migrate. Proliferation of mAPCs was observed on day 5 and the cells had reached sub-confluence by day 7, but were still positive for nestin. On day 3 of culture the mAPCs were also positive for E-cadherin, an epithelial cell marker, and vimentin, a marker for mesenchymal cells. On day 5, E-cadherin expression remained in cells that adhered with each other, but had disappeared in migrating cells, which still expressed vimentin. These results suggest an epithelial to mesenchymal transition. Further work showed that mAPCs can play an important role of pancreatic carcinogenesis.

胰腺干细胞缝隙和肿瘤干细胞在胰腺癌发生中的作用一直难以捉摸。我们研究了小鼠胰腺上皮细胞在生长因子刺激下的去分化能力。我们观察到在含有血清和/或生长因子的明胶培养皿中培养的小鼠胰腺外植体中形成具有间充质表型的细胞；我们将这些细胞称为MAPC(鼠腺泡来源的胰腺细胞)。培养第1天，大多数细胞形成高水平淀粉酶的腺泡细胞团。到第3天，已形成球状细胞聚集体，具有成纤维细胞样形态的细胞(MAPC)开始迁移，淀粉酶和巢蛋白阳性。第5天可见MAPC增殖，第7天细胞已达到亚融合状态，但Nestin仍呈阳性反应。培养第3天，MAPC上皮细胞标记物E-钙粘附素和间质细胞标记物Vimentin阳性。第5天，E-钙粘蛋白在相互粘连的细胞中仍有表达，但在迁移细胞中已消失，仍表达波形蛋白。这些结果提示上皮细胞向间质细胞的转变。进一步的研究表明MAPC在胰腺癌的发生中起重要作用。