MT4‐MMP in tumor‐associated macrophages is linked to hepatocellular carcinoma aggressiveness and recurrence
MT4‐MMP in tumor‐associated macrophages is linked to hepatocellular carcinoma aggressiveness and recurrence
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肿瘤相关巨噬细胞中的 MT4-MMP 与肝细胞癌的侵袭性和复发有关
DOI：
10.1002/ctm2.162
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发表时间：
2020-08
影响因子：
10.6
通讯作者：
Jinglin Xia
中科院分区：
文献类型：
--
作者：
Feng Qi;Jia Li;Mengzhou Guo;Biwei Yang;Jinglin Xia
肝细胞癌（HCC）是人类最致命的癌症之一，排在第五位最常见的原发性癌症和第三位最常见的癌症相关死亡原因。1近年来，肿瘤微环境被认为与耐药性和肿瘤复发密切相关。2它包括炎性细胞，癌细胞，和细胞外基质（ECM）。3巨噬细胞的极化和表型转变是肿瘤相关慢性炎症的主要特征。4肿瘤相关巨噬细胞（TAM）显示M2样表型并密切参与肿瘤发生，转移、ECM重塑和低表达。5 MT4-MMP（也称为MMP 17），作为ECM重塑物的MMP家族的成员，通过糖基磷脂酰肌醇锚（GPI）6被膜锚定，并直接分解一组特定的底物，如纤维蛋白原、proTNF、ADAMTS 4、和αM整联蛋白。7据报道，MT4-MMP由巨噬细胞表达，并与炎症和血管生成有关。8特别是，最近在胃肠腺癌、前列腺癌、骨肉瘤、白血病、肺癌、胶质母细胞瘤、宫颈癌、黑色素瘤和乳腺癌中观察到MT4-MMP转录物。9然而，MT4-MMP在HCC中的作用仍然知之甚少。我们探讨了MT4-MMP在人HCC中的表达谱。分别通过qPCR和蛋白质印迹分析43对和12对瘤周组织和肿瘤组织。总生存期（OS）是从手术到死亡或最终随访的时间，而无复发生存期（RFS）定义为手术和复发之间的时间间隔。数据显示，MT4-MMP mRNA和蛋白质水平在肿瘤周围组织中比在肿瘤组织中明显上调（图1A和B）。接下来，通过免疫组织化学进一步分析316对配对的瘤周和肿瘤组织的MT4-MMP表达（图1C）。患者临床和人口统计学特征汇总于表S1中。
Dear Editor, Hepatocellular carcinoma (HCC) is among the deadliest human cancers, ranking as the fifth most common primary cancer and the thirdmost commoncancer-associated cause of death.1 The tumor microenvironment has been proposed in recent years to be closely related to resistance and tumor recurrence.2 It includes inflammatory cells, cancer cells, and extracellular matrix (ECM).3 Polarization and phenotypic transition of macrophages are the primary features of tumor-associated chronic inflammation.4 Tumor-associated macrophages (TAMs) show an M2-like phenotype and are closely involved in tumorigenesis, metastasis, ECM remodeling, and poor prognosis.5 MT4-MMP (also named MMP17), as a member of the MMP family of ECM remodelers, is membrane anchored by a glycosylphosphatidylinositol anchor (GPI)6 and directly resolves a specific set of substrates, such as fibrinogen, proTNF, ADAMTS4, and αM integrin.7 MT4-MMP has been reported to be expressed by macrophages and to be associated with inflammation and angiogenesis.8 In particular, the MT4-MMP transcript was recently observed in gastrointestinal adenocarcinomas, prostate cancer, osteosarcomas, leukemias, lung carcinomas, glioblastomas, cervical carcinomas, melanomas, and breast cancer.9 However, the role of MT4-MMP in HCC is still poorly understood. We explored the MT4-MMP expression profile in human HCC. Forty-three and 12 pairs peritumoral and tumor tissues, respectively, were analyzed by qPCR and western blot. Overall survival (OS) was the time from surgery to death or final follow-up, while recurrencefree survival (RFS) was defined as the interval between surgery and recurrence. Data revealed that the MT4-MMP mRNA and protein level was obviously upregulated in peritumoral tissues over tumor tissues (Figure 1A and B). Next, 316 paired peritumoral and tumor tissues were further analyzed for MT4-MMP expression by immunohistochemistry (Figure 1C). Patient clinical and demographic characteristics are compiled in Table S1.
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DOI：
10.1007/s00018-014-1796-8
发表时间：
2015-04
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
McWhorter FY;Davis CT;Liu WF
通讯作者：
Liu WF
影响因子：
5.6
作者：
C. Yip;P. Foidart;A. Noël;N. Sounni
通讯作者：
C. Yip;P. Foidart;A. Noël;N. Sounni
DOI：
--
发表时间：
--
期刊：
--
影响因子：
--
作者：
D. Hanahan;L. Coussens
通讯作者：
D. Hanahan;L. Coussens
DOI：
10.1038/nri2448
发表时间：
2008-12
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
20.1
作者：
Martin-Alonso, Mara;Garcia-Redondo, Ana B.;Arroyo, Alicia G.
通讯作者：
Arroyo, Alicia G.