Identification of tumorigenic retinal stem‐like cells in human solid retinoblastomas
Identification of tumorigenic retinal stem‐like cells in human solid retinoblastomas
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DOI：
10.1002/ijc.22880
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发表时间：
2007-11
影响因子：
6.4
通讯作者：
X. Zhong;Yongping Li;Fuhua Peng;Bing Huang;Jian-xian Lin;Wenxin Zhang;Jian-liang Zheng;Ruzhang Jiang;Ge Song;J. Ge
中科院分区：
文献类型：
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作者：
X. Zhong;Yongping Li;Fuhua Peng;Bing Huang;Jian-xian Lin;Wenxin Zhang;Jian-liang Zheng;Ruzhang Jiang;Ge Song;J. Ge
视网膜母细胞瘤（RB）是儿童视网膜最常见的恶性肿瘤。虽然长期以来一直假设RB来源于多能视网膜干细胞（RSC）或成视网膜细胞，但RB肿瘤中存在致瘤性RSC的直接证据仍然缺乏。一些研究表明，恶性肿瘤含有与其正常组织干细胞对应物相似的肿瘤干细胞。通过体外培养和分化方法，我们证明了致瘤性视网膜干细胞样细胞（RSLC）确实存在于RB病变中，并且RB肿瘤源性培养物包含能够作为克隆非粘附神经球广泛增殖的未分化细胞，并且可以在体外分化为不同的视网膜细胞。有趣的是，培养的细胞表达视网膜发育相关基因，包括巢蛋白，CD 133，pax 6，chx 10和Rx，并过表达Bmi-1，一种干细胞自我更新和增殖所需的基因。值得注意的是，当这些培养的细胞被眼内移植到SCID小鼠，它们产生了新的肿瘤，其组织形态学特征和免疫表型与其亲本原发性RB相似。结果表明，RB含有促肿瘤发生的RSLC。本研究为探讨RB的组织发生提供了新的思路，并为其他RB的研究建立了模型。© 2007 Wiley利斯公司
Retinoblastoma (RB) is the most common malignant tumor of the retina in human children. Although it has been hypothesized for a long time that RB derives from multipotent retinal stem cells (RSCs) or retinoblasts, the direct evidence that the presence of tumorigenic RSCs in RB tumors is still lacking. Some studies indicate that malignant tumors contain tumor stem cells similar to their normal tissue stem cell counterparts. With in vitro culture and differentiation method we demonstrate that tumorigenic retinal stem‐like cells (RSLCs) indeed exist in RB lesions and that RB tumor‐derived cultures encompass undifferentiated cells capable of extensive proliferation as clonal nonadherent neurospheres and can differentiate into different retinal cells in vitro. Interestingly, cultured cells expressed retinal development related genes including nestin, CD133, pax6, chx10 and Rx, and overexpressed Bmi‐1, a gene required for self‐renewal and proliferation of stem cells. Significantly, when these cultured cells were intraocularly transplanted into SCID mice, they gave rise to new tumors with histomorphological features and immunophenotypes similar to their parental primary RBs. The results show that RBs contain tumorigenic RSLCs that contribute to tumorigenesis. This study provides a new insight to investigate the histogenesis of RBs and establishes a model for other RB research. © 2007 Wiley‐Liss, Inc.