Fibroblasts-dependent Invasion of Podoplanin-Positive Cancer Stem Cells in Squamous Cell Carcinoma
Fibroblasts-dependent Invasion of Podoplanin-Positive Cancer Stem Cells in Squamous Cell Carcinoma
复制标题
鳞状细胞癌中平足蛋白阳性癌症干细胞的成纤维细胞依赖性侵袭
DOI：
10.1002/jcp.29624
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Ishii G.
中科院分区：
文献类型：
--
作者：
Miyashita T;Neri S;Hashimoto H;Akutsu A;Sugano M;Fujii S;Ochiai A;Ishii G.
目的：明确在成纤维细胞依赖的侵袭过程中，鳞状细胞癌中podoplanin阳性肿瘤干细胞是否具有更高的侵袭活性。采用荧光泛素化为基础的细胞周期指示剂标记的A431细胞进行胶原凝胶侵袭试验。采用延时成像技术与成纤维细胞共培养，计数S/G2/M期浸润细胞的总数和数量。当成纤维细胞不存在时，侵袭podoplanin阳性和阴性A431细胞的数量无显著差异。相反，当成纤维细胞存在时，入侵podoplanin阳性细胞的数量明显增加。侵袭间S/G2/M期细胞出现频率无差异。当成纤维细胞存在时，敲低podoplanin可显著减少A431细胞的入侵数量。当成纤维细胞存在时，Podoplanin阳性的A431细胞表现出更高的侵袭活性，这表明癌症干细胞的一些生物学功能可能仅在纤维性肿瘤微环境中才显现出来。
To clear whether podoplanin‐positive cancer stem cells in squamous cell carcinoma have higher invasion activity during a fibroblasts‐dependent invasion. A collagen gel invasion assay was performed using fluorescent ubiquitination‐based cell cycle indicator‐labeled A431 cells. The total number and number of invading cells in S/G2/M phase were counted using time‐lapse imaging cocultured with fibroblasts. There was no significant difference between the number of invading podoplanin‐positive and negative A431 cells when fibroblasts did not exist. On the contrary, the number of invading podoplanin‐positive cells was significantly higher when fibroblasts existed. The frequency of cells in S/G2/M phase among invasion was no difference. Knockdown of podoplanin decreased the number of invaded A431 cells significantly when fibroblasts existed. Podoplanin‐positive A431 cells display higher invasion activity when fibroblasts exist, suggesting that some biological functions of cancer stem cells might become evident only within the fibrous tumor microenvironment.