a Department of General Surgery , Shanghai Tenth Peoples' Hospital affiliated Tongji University , No. 301, Middle Yanchang Road, Shanghai , China.
b Department of Pathology , Dahua Hospital, No. 901, Old Humin Road, Xuhui District, Shanghai , China.
Cancer Biol Ther. 2017 Oct 3;18(10):806-815. doi: 10.1080/15384047.2017.1373219. Epub 2017 Sep 21.
It was well known that cancer-associated fibroblasts (CAFs) were an essential factor in tumor progression. However, the actual mechanism of stromal fibroblasts activation and tumor promoting effects remain unclear. Here, we showed that KLF5 expression was more frequently observed in gastric cancer-associated fibroblasts compared with normal mucosal fibroblasts. Moreover, KLF5 expression in tumor stroma was closely associated with clinicopathological features such as tumor size, invasion depth, cell grade and lymph node metastasis, as well as poor prognosis in patients with gastric cancer. In addition, we further demonstrated that KLF5-regulating CAFs affect gastric cancer cells progression by CCL5 secretion and activation of CCR5. Taken together, we concluded that KLF5 expression in gastric cancer-associated fibroblasts contribute to poor survival and promote cancer cells progression by activation of CCL5/CCR5 axis, which suggesting that KLF5 in CAFs might be considered as a promising target for the treatment of gastric cancer.
众所周知，癌症相关成纤维细胞（CAFs）是肿瘤进展的重要因素。然而，基质成纤维细胞激活和促进肿瘤的实际机制仍不清楚。在这里，我们发现与正常黏膜成纤维细胞相比，KLF5 在胃癌相关成纤维细胞中的表达更为频繁。此外，肿瘤基质中 KLF5 的表达与临床病理特征密切相关，如肿瘤大小、浸润深度、细胞分级和淋巴结转移，以及胃癌患者的预后不良。此外，我们进一步证明，KLF5 调节的 CAFs 通过 CCL5 分泌和 CCR5 的激活影响胃癌细胞的进展。综上所述，我们得出结论，胃癌相关成纤维细胞中的 KLF5 表达通过激活 CCL5/CCR5 轴促进不良生存和促进癌细胞进展，这表明 CAFs 中的 KLF5 可能被认为是治疗胃癌的有前途的靶点。
