Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling.
Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling.
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DOI：
10.1016/j.cell.2013.09.031
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发表时间：
2013-10-10
期刊：
影响因子：
64.5
通讯作者：
Karin M
中科院分区：
文献类型：
--
作者：
He G;Dhar D;Nakagawa H;Font-Burgada J;Ogata H;Jiang Y;Shalapour S;Seki E;Yost SE;Jepsen K;Frazer KA;Harismendy O;Hatziapostolou M;Iliopoulos D;Suetsugu A;Hoffman RM;Tateishi R;Koike K;Karin M
肝细胞癌（HCC）是一种缓慢发展的恶性肿瘤，被认为是由慢性损伤肝脏的癌前病变演变而来。然而，从未确定癌前病变实际上含有引起癌症的肿瘤祖细胞。在这里，我们描述了从不同的小鼠HCC模型中分离和鉴定HCC祖细胞（HcPCs）。与完全恶性的HCC不同，HcPC仅在引入经历慢性损伤和代偿性增殖的肝脏时才引起癌症。虽然HCPCs表现出类似的转录谱的双能肝胆祖细胞，后者不引起肿瘤。类似HcPC的细胞存在于HCC结节前几个月出现的发育不良病变中。与早期肝癌发生不同，其依赖于炎性细胞的旁分泌IL-6产生，由于LIN 28表达的上调，HcPC获得了刺激其体内生长和恶性进展的自分泌IL-6信号传导。这可能是驱动其他产生IL-6的恶性肿瘤的一般机制。
Hepatocellular carcinoma (HCC) is a slowly developing malignancy postulated to evolve from pre-malignant lesions in chronically damaged livers. However, it was never established that premalignant lesions actually contain tumor progenitors that give rise to cancer. Here, we describe isolation and characterization of HCC progenitor cells (HcPCs) from different mouse HCC models. Unlike fully malignant HCC, HcPCs give rise to cancer only when introduced into a liver undergoing chronic damage and compensatory proliferation. Although HcPCs exhibit a similar transcriptomic profile to bipotential hepatobiliary progenitors, the latter do not give rise to tumors. Cells resembling HcPCs reside within dysplastic lesions that appear several months before HCC nodules. Unlike early hepatocarcinogenesis, which depends on paracrine IL-6 production by inflammatory cells, due to upregulation of LIN28 expression, HcPCs had acquired autocrine IL-6 signaling that stimulates their in vivo growth and malignant progression. This may be a general mechanism that drives other IL-6-producing malignancies.
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影响因子：
1.8
作者：
Mikhail S;He AR
通讯作者：
He AR
影响因子：
64.5
作者：
Hatziapostolou M;Polytarchou C;Aggelidou E;Drakaki A;Poultsides GA;Jaeger SA;Ogata H;Karin M;Struhl K;Hadzopoulou-Cladaras M;Iliopoulos D
通讯作者：
Iliopoulos D
影响因子：
6
作者：
Laconi, E;Oren, R;Shafritz, DA
通讯作者：
Shafritz, DA
影响因子：
10.5
作者：
Dorrell, Craig;Erker, Laura;Grompe, Markus
通讯作者：
Grompe, Markus
DOI：
10.1056/nejmoa0901282
发表时间：
2009-10-08
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ji J;Shi J;Budhu A;Yu Z;Forgues M;Roessler S;Ambs S;Chen Y;Meltzer PS;Croce CM;Qin LX;Man K;Lo CM;Lee J;Ng IO;Fan J;Tang ZY;Sun HC;Wang XW
通讯作者：
Wang XW