Cell-surface Vimentin: A mislocalized protein for isolating csVimentin(+) CD133(-) novel stem-like hepatocellular carcinoma cells expressing EMT markers.
Cell-surface Vimentin: A mislocalized protein for isolating csVimentin(+) CD133(-) novel stem-like hepatocellular carcinoma cells expressing EMT markers.
复制标题
细胞表面波形蛋白：一种用于分离csvimentin（+）CD133（ - ）新型茎状的肝细胞癌细胞的氯定位蛋白，表达EMT标记。
DOI：
10.1002/ijc.29382
复制
发表时间：
2015-07-15
影响因子：
6.4
通讯作者：
Li, Shulin
中科院分区：
文献类型：
--
作者：
Mitra, Abhisek;Satelli, Arun;Xia, Xueqing;Cutrera, Jeffrey;Mishra, Lopa;Li, Shulin
肿瘤干细胞生物学的最新进展表明，具有上皮-间充质转化(EMT)表型的肿瘤干细胞更具侵袭性并导致复发；然而，由于缺乏分离这些EMT干细胞的特异性标记，阻碍了这一方向的研究。细胞表面标志物已被用于分离肿瘤干细胞样细胞，但尚未发现用于分离具有EMT表型的肿瘤干细胞样细胞。最近，我们发现Vimentin是一种细胞内EMT肿瘤细胞标志物，存在于肝脏结肠转移瘤结节的表面。在这项研究中，我们通过使用一种特异性的CSV结合抗体84-1来检测靶向细胞表面波形蛋白(CSV)分离具有EMT表型的干细胞的可能性。使用该抗体，我们从原代肝肿瘤细胞悬液中纯化了CSV阳性、CD133阴性(CSVim+CD133−)细胞群，并对其干细胞特性进行了鉴定。球体鉴定和干细胞标志物Sox2和Oct4A染色的结果表明，csVim+CD133−细胞具有与csVim−CD133+群体相似的干细胞样特性。我们的研究进一步揭示了csVim+CD133−细胞具有EMT表型，表现为细胞核中存在扭曲和鼻塞，细胞表面不存在EpCAM，上皮标志物E-钙粘素的表达水平处于基础水平。CsVimentin阴性的CD133阳性干细胞不具有任何EMT表型。CsVim+CD133+−细胞较csVim+−CD133+细胞具有更强的肝脏转移能力。我们的研究结果表明，csVim+CD133−细胞是治疗和预防转移性肝细胞癌的有前途的靶点。
Recent advances in cancer stem cell biology have shown that cancer stem–like cells with epithelial–mesenchymal transition (EMT) phenotypes are more aggressive and cause relapse; however absence of a specific marker to isolate these EMT stem-like cells hampers research in this direction. Cell surface markers have been identified for isolating cancer stem-like cells, but none has been identified for isolating cancer stem-like cells with EMT phenotype. Recently, we discovered that Vimentin, an intracellular EMT tumor cell marker, is present on the surface of colon metastatic tumor nodules in the liver. In this study, we examined the potential of targeting cell surface Vimentin (CSV) to isolate stem-like cancer cells with EMT phenotype, by using a specific CSV-binding antibody, 84-1. Using this antibody, we purified the CSV positive, CD133-negative (csVim+CD133−) cell population from primary liver tumor cell suspensions and characterized for stem cell properties. The results of sphere assays and staining for the stem cell markers Sox2 and Oct4A demonstrated that csVim+CD133− cells have stem-like properties similar to csVim−CD133+ population. Our investigation further revealed that the csVim+CD133− cells had EMT phenotypes, as evidenced by the presence of Twist and Slug in the nucleus, the absence of EpCAM on the cell surface and basal level of expression of epithelial marker E-cadherin. The csVimentin negative CD133 positive stem cells do not have any EMT phenotypes. csVim+CD133− cells exhibited more aggressively metastatic in livers than csVim−CD133+ cells. Our findings indicate that csVim+CD133− cells are promising targets for treatment and prevention of metastatic hepatocellular carcinoma.
登录
查看更多内容
影响因子：
17.3
作者：
Mitra A;Mishra L;Li S
通讯作者：
Li S
影响因子：
11.2
作者：
Hollier BG;Tinnirello AA;Werden SJ;Evans KW;Taube JH;Sarkar TR;Sphyris N;Shariati M;Kumar SV;Battula VL;Herschkowitz JI;Guerra R;Chang JT;Miura N;Rosen JM;Mani SA
通讯作者：
Mani SA
影响因子：
37.3
作者：
Nagy ZS;LeBaron MJ;Ross JA;Mitra A;Rui H;Kirken RA
通讯作者：
Kirken RA
影响因子：
9
作者：
Chang, L.;Graham, P. H.;Hao, J.;Ni, J.;Bucci, J.;Cozzi, P. J.;Kearsley, J. H.;Li, Y.
通讯作者：
Li, Y.
影响因子：
23.9
作者：
Lee, Terence Kin Wah;Castilho, Antonia;Irene Oi Lin Ng
通讯作者：
Irene Oi Lin Ng