Cancer-associated fibroblasts from hepatocellular carcinoma promote malignant cell proliferation by HGF secretion.
Cancer-associated fibroblasts from hepatocellular carcinoma promote malignant cell proliferation by HGF secretion.
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肝细胞癌中的癌症相关成纤维细胞通过 HGF 分泌促进恶性肿瘤细胞增殖
DOI：
10.1371/journal.pone.0063243
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhang Q
中科院分区：
文献类型：
--
作者：
Jia CC;Wang TT;Liu W;Fu BS;Hua X;Wang GY;Li TJ;Li X;Wu XY;Tai Y;Zhou J;Chen GH;Zhang Q
据报道，癌症相关成纤维细胞（CAF）通过刺激大多数实体瘤中的血管生成、癌细胞增殖和侵袭来支持肿瘤发生。然而，CAF 在肝癌微环境中的作用尚未得到深入研究。在我们前期的研究中，我们成功地从肝细胞癌（HCC）中分离出CAF（H-CAF），并证明H-CAF抑制NK细胞的活化，从而为HCC进展创造了有利条件。在我们目前的研究中，我们发现用 H-CAF 的条件培养基处理可显着促进 MHCC97L 和 Hep3B 细胞的增殖。病理分析还表明，H-CAFs增加了Ki-67（+）恶性细胞的比例并防止它们坏死。此外，H-CAF的条件培养基中肝细胞生长因子（HGF）细胞因子的浓度高于正常皮肤成纤维细胞（NSF）的条件培养基。抗HGF显着降低H-CAF的增殖促进能力。此外，我们发现 H-CAF 的丰度与肿瘤大小呈正相关。这些结果表明H-CAFs是体内外促进HCC生长的重要因素，并且HGF在H-CAFs诱导的HCC增殖中发挥着关键作用。
Cancer-associated fibroblasts (CAFs) are reported to support tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and invasion in most solid tumors. However, the roles of CAFs in the liver cancer microenvironment have not been thoroughly studied. In our previous study, we successfully isolated CAFs from hepatocellular carcinoma (HCC) (H-CAFs) and proved that H-CAFs suppressed the activation of NK cells and thereby created favorable conditions for HCC progression. In our present study, we found that the proliferation of MHCC97L and Hep3B cells was significantly promoted by treatment with conditioned medium from H-CAFs. Pathological analysis also revealed that H-CAFs increased the proportion of Ki-67 (+) malignant cells and prevented them from undergoing necrosis. Moreover, the concentration of hepatocyte growth factor (HGF) cytokine in the conditioned medium of H-CAFs was higher than conditioned medium from normal skin fibroblasts (NSFs). Anti-HGF significantly reduced the proliferation-promoting capability of H-CAFs. In addition, we found that the abundance of H-CAFs correlated positively with tumor size. These results indicate that H-CAFs are an important factor for promoting the growth of HCC in vitro and in vivo, and that HGF plays a key role in HCC proliferation induced by H-CAFs.
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