Tumor-associated macrophage or chemokine ligand CCL17 positively regulates the tumorigenesis of hepatocellular carcinoma
Tumor-associated macrophage or chemokine ligand CCL17 positively regulates the tumorigenesis of hepatocellular carcinoma
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肿瘤相关巨噬细胞或趋化因子配体CCL17正向调控肝细胞癌的发生
DOI：
10.1007/s12032-016-0729-9
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发表时间：
2016-01
期刊：
影响因子：
3.4
通讯作者：
Luo Fang
中科院分区：
文献类型：
--
作者：
Zhu Fangyu;Li Xiangnan;Chen Siyu;Zeng Qiu;Zhao Yu;Luo Fang
另外，活化的巨噬细胞（M2）可以分泌趋化因子，如趋化因子配体17（CCL 17），并与促进肝细胞癌（HCC）的肿瘤发生有关。本研究旨在研究M2和CCL 17在HCC进展中的潜在作用。通过组织芯片对90例HCC标本中CCL 17的表达水平进行表征，并对术后生存率进行分层。将MHCC 97 L细胞与经典活化的M1、M2或CCL 17沉默的M2 ccl 17突变体共培养或用来自这些细胞的条件培养基（CM）或CCL 17处理。体外观察MHCC 97 L细胞的伤口愈合、侵袭能力、存活率和凋亡情况，体内观察肿瘤生长情况。采用细胞球形成法、流式细胞术和Western blot检测MHCC 97 L细胞的干细胞性。测定上皮-间质转化（EMT）因子和Wnt/β-catenin信号的相对表达水平。CCL 17在肝癌组织中的高表达与肝癌的临床病理特征及患者的生存率相关（P< 0.05）。在MHCC 97 L细胞中检测到高水平的CCR 4。用来自M2的CM或用CCL 17处理显著增强MHCC 97 L细胞的伤口愈合过程、侵袭和增殖。M2与MHCC 97 L细胞共移植可显著促进MHCC 97 L肿瘤的生长。与M2共培养或CCL 17处理可增强MHCC 97 L细胞的干细胞性、EMT过程、TGF-β1和Wnt/β-catenin信号通路。CCL 17可促进肝癌的发生发展，可能成为肝癌预后和治疗的潜在生物标志物和靶点。
Alternatively activated macrophages (M2) can secrete chemokines, such as chemokine ligand 17 (CCL17), and are associated with promoting tumorigenesis of hepatocellular carcinoma (HCC). This study aimed at investigating the potential role of M2 and CCL17 in progression of HCC. The levels of CCL17 expression in 90 HCC samples were characterized by tissue microarray and stratified for the postsurgical survival. MHCC97L cells were co-cultured with classically activated M1, M2 or CCL17-silencing M2ccl17muteor treated with conditional medium (CM) from these cells or CCL17 in vitro. The wound healing, invasion, viability and apoptosis of MHCC97L cells in vitro and tumor growth in vivo were determined. The stemness of MHCC97L cells was examined by sphere formation, flow cytometry and Western blot. The relative expression levels of epithelial–mesenchymal transition (EMT) factors and the Wnt/β-catenin signaling were determined. Higher levels of intratumoral CCL17 expression were significantly associated with clinical pathological characteristics of HCC and with poorer overall survival rates in HCC patients (P< 0.05). High levels of CCR4 were detected in MHCC97L cells. Treatment with the CM from M2 or with CCL17 significantly enhanced the wound healing process, invasion and proliferation of MHCC97L cells in vitro. Co-implantation MHCC97L cells with M2 significantly promoted the growth of MHCC97L tumors in vivo. Co-culture with M2 or treatment with CCL17 enhanced the stemness, EMT process, the TGF-β1 and Wnt/β-catenin signaling in MHCC97L cells. CCL17 promotes the tumorigenesis of HCC and may be a potential biomarker and target for HCC prognosis and therapy.
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影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
50.3
作者：
Magee JA;Piskounova E;Morrison SJ
通讯作者：
Morrison SJ
影响因子：
13.5
作者：
Chiba, Tetsuhiro;Kita, Kaoru;Taniguchi, Hideki
通讯作者：
Taniguchi, Hideki
DOI：
10.1186/s13058-014-0408-8
发表时间：
2014-07-24
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Zhao Z;Lu P;Zhang H;Xu H;Gao N;Li M;Liu C
通讯作者：
Liu C
DOI：
10.1038/nrm3758
发表时间：
2014-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
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