MIF, secreted by human hepatic sinusoidal endothelial cells, promotes chemotaxis and outgrowth of colorectal cancer in liver prometastasis.
MIF, secreted by human hepatic sinusoidal endothelial cells, promotes chemotaxis and outgrowth of colorectal cancer in liver prometastasis.
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MIF由人肝窦内皮细胞分泌，促进结直肠癌肝转移中的趋化性和生长
DOI：
10.18632/oncotarget.4198
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发表时间：
2015-09-08
期刊：
影响因子：
--
通讯作者：
Ding YQ
中科院分区：
文献类型：
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作者：
Hu CT;Guo LL;Feng N;Zhang L;Zhou N;Ma LL;Shen L;Tong GH;Yan QW;Zhu SJ;Bian XW;Lai MD;Deng YJ;Ding YQ
肝脏中转移性结直肠癌（CRC）细胞的生长和侵袭取决于微环境。在这里，我们发现人肝窦内皮细胞 (HHSEC) 诱导 CRC 细胞的趋化性和生长。 HHSEC 释放的巨噬细胞迁移抑制因子 (MIF) 刺激 CRC 细胞的趋化性。 MIF 由 HHSEC 分泌，但不是由 CRC 细胞本身分泌，促进迁移和上皮间质转化 (EMT)，并促进 CRC 细胞的增殖和凋亡抵抗。在裸鼠原位植入模型中，外源性 MIF 刺激 CRC 细胞的生长和转移。此外，MIF 通过抑制 F-肌动蛋白解聚和磷酸化丝切蛋白来加速 CRC 细胞的迁移性。值得注意的是，MIF 水平与肝转移瘤的大小相关。我们认为 HHSEC 和旁分泌 MIF 促进肝窦中 CRC 细胞的初始迁移和增殖，从而产生肝转移。
Growth and invasion of metastatic colorectal cancer (CRC) cells in the liver depend on microenvironment. Here, we showed that human hepatic sinusoidal endothelial cells (HHSECs) induce chemotaxis and outgrowth of CRC cells. Macrophage migration inhibitory factor (MIF), released by HHSECs, stimulated chemotaxis of CRC cells. MIF secreted by HHSECs, but not by CRC cells themselves, promoted migration and epithelial-mesenchymal transition (EMT) and facilitated proliferation and apoptotic resistance of CRC cells. In orthotopic implantation models in nude mice, exogenous MIF stimulated growth of CRC cells and metastasis. Furthermore, MIF accelerated mobility of CRC cells by suppressing F-actin depolymerization and phosphorylating cofilin. Noteworthy, MIF levels were correlated with the size of hepatic metastases. We suggest that HHSECs and paracrine MIF promote initial migration and proliferation of CRC cells in the hepatic sinusoids to generate liver metastases.