Cancer Cell Biology

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Identification of tumorigenic retinal stem-like cells in human solid retinoblastomas

  1. Xiufeng Zhong1,†,
  2. Yongping Li1,†,
  3. Fuhua Peng2,
  4. Bing Huang1,
  5. Jianxian Lin1,
  6. Wenxin Zhang1,
  7. Jianliang Zheng1,
  8. Ruzhang Jiang1,
  9. Ge Song1,
  10. Jian Ge1,‡,*

Article first published online: 12 JUN 2007

DOI: 10.1002/ijc.22880

Issue

International Journal of Cancer

International Journal of Cancer

Volume 121, Issue 10, pages 2125–2131, 15 November 2007

Additional Information

How to Cite

Zhong, X., Li, Y., Peng, F., Huang, B., Lin, J., Zhang, W., Zheng, J., Jiang, R., Song, G. and Ge, J. (2007), Identification of tumorigenic retinal stem-like cells in human solid retinoblastomas. Int. J. Cancer, 121: 2125–2131. doi: 10.1002/ijc.22880

Author Information

  1. 1

    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China

  2. 2

    The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

  1. †

    The first two authors contributed equally to this paper.

  2. ‡

    Fax: +8620-87333271.

*State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center of Sun Yat-Sen University, Xianlie South Road 54, 510060 Guangzhou, China

Publication History

  1. Issue published online: 25 SEP 2007
  2. Article first published online: 12 JUN 2007
  3. Manuscript Accepted: 24 APR 2007
  4. Manuscript Received: 26 NOV 2006

Funded by

  • National Natural Science Foundation of China. Grant Numbers: 30200308, 30300380, 30672276
  • Fund for Innovative Research Groups of China. Grant Number: 3031004
  • Science and technology Project of Guangdong Province. Grant Number: 2006B36006007

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Keywords:

  • retinoblastoma;
  • tumor stem cell;
  • retinal stem cell;
  • tumorigenesis

Abstract

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.

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