Tumor necrosis factor alpha induces myofibroblast differentiation in human tongue cancer and promotes invasiveness and angiogenesis via secretion of stromal cell-derived factor-1
Tumor necrosis factor alpha induces myofibroblast differentiation in human tongue cancer and promotes invasiveness and angiogenesis via secretion of stromal cell-derived factor-1
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肿瘤坏死因子 α 诱导人舌癌肌成纤维细胞分化，并通过分泌基质细胞衍生因子 1 促进侵袭性和血管生成
DOI：
10.1016/j.oraloncology.2015.08.017
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发表时间：
2015
期刊：
影响因子：
4.8
通讯作者：
Chen Wei-Liang
中科院分区：
文献类型：
--
作者：
Zhou Bin;Zhuang Xiu-Mei;Wang You-Yuan;Lin Zhao-Yu;Zhang Da-Ming;Fan Song;Li Jin-Song;Chen Wei-Liang
目的：癌相关成纤维细胞（CAFs）在肿瘤进展中起重要作用，与预后不良有关。肿瘤坏死因子α（TNFα）参与了多种肿瘤的生长和转移，并与上皮间质转化（EMT）有关。材料与方法本实验采用原代培养的舌鳞癌成纤维细胞（CAFs）和正常成纤维细胞（NFs）配对，并分别用TNFα和CAFs衍生的基质细胞衍生因子-1（SDF 1）处理两株TSCC细胞系SCC 9和CAL 27，观察其体外侵袭和EMT的变化。另外，用TNFα处理NFs以检测肌成纤维细胞标志物的表达、侵袭性、诱导的胶原凝胶收缩和增强的癌转移。结果TNF α和CAFs来源的SDF 1分别诱导TSCC细胞的侵袭和EMT，TNF α和CAFs来源的SDF 1分别诱导TSCC细胞的侵袭和EMT。TNFα促进NFs向CAFs样成纤维细胞转化，并获得与CAFs相似的肌成纤维细胞标志物表达和恶性功能。结论TNFα可能通过分泌SDF 1促进舌癌成肌纤维细胞分化，从而直接或间接促进舌癌转移、EMT和血管生成。
ObjectivesCancer-associated fibroblasts (CAFs) play an important role in tumor progression and are associated with a poor prognosis. Tumor necrosis factor α (TNFα) has been involved in growth and metastasis associated with epithelial–mesenchymal transition (EMT) in many types of cancers. However, the relationship among the TNFα, activation of CAFs and their tumor-promoting effects on tongue squamous cell carcinoma (TSCC) remain obscure.Materials and methodsA series of matched primary CAFs and normal fibroblasts (NFs) pairs were cultured, and additionally two TSCC cell lines SCC9 and CAL27, were treated with TNFα or CAFs derived stromal cell-derived factor-1 (SDF1) respectively to study invasion and EMTin vitro. In addition, NFs were treated with TNFα to detect the expression of myofibroblast markers, invasion, induced collagen gel contraction and enhanced cancer metastasis. Finally, invasion and angiogenesis of human vein endothelial cells (HUVECs) treated with TNFα and CAFs derived SDF1 was measured.ResultsTNFα and CAFs-derived SDF1 induced TSCC cells metastasis and EMT separately. TNFα facilitated the transformation of NFs to CAFs-like fibroblasts, which was accompanied by acquisition of similar myofibroblast markers expression and malignant function to CAFs. Furthermore, TNFα and CAFs derived SDF1 also promoted invasion and angiogenesis of HUVECs.ConclusionThese results suggest that TNFα may not only directly but also indirectly enhance cancer metastasis, EMT and angiogenesis formation in tongue cancer through myofibroblast differentiation via SDF1 secretion.