MIF, secreted by human hepatic sinusoidal endothelial cells, promotes chemotaxis and outgrowth of colorectal cancer in liver prometastasis
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Chun-Ting Hu1,2, Li-Li Guo1,2, Na Feng1,2, Lei Zhang3, Na Zhou1, Li-Li Ma1, Lan Shen1, Gui-Hui Tong1, Qian-Wen Yan1, Shi-Jie Zhu1, Xiu-Wu Bian4, Mao-De Lai5, Yong-Jian Deng1,2, Yan-Qing Ding1,2
1Department of Pathology, Nanfang Hospital and School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
2Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, China
3Department of General Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China
4Department of Pathology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
5Department of Pathology, School of Medical Sciences, Zhejiang University, Hangzhou 310006, China
Yong-Jian Deng, e-mail: [email protected]
Yan-Qing Ding, e-mail: [email protected]
Keywords: colorectal cancer, hepatic sinusoidal endothelial cell, macrophage migration inhibitory factor, chemotaxis, metastasis
Received: March 03, 2015 Accepted: May 20, 2015 Published: June 02, 2015
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.
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