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Incorporation of endothelial progenitor cells into the neovasculature of malignant glioma xenograft

  • Laboratory investigation - human/animal tissue
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Abstract

Endothelial progenitor cells (EPCs) are important initiators of vasculogenesis in the process of tumor neovascularization. However, it is unclear how circulating EPCs contribute to the formation of tumor microvessels. In this study, we isolated CD34+/CD133+ cells from human umbilical cord blood (HUCB) and obtained EPCs with the capacities of forming colonies, uptaking acetylated low-density lipoprotein (ac-LDL), binding lectins and expressing vascular endothelial growth factor (VEGF) receptor 2 (VEGFR-2, KDR), CD31 and von Willebrand factor (vWF). These EPCs were actively proliferative and migratory, and could formed capillary-like tubules in response to VEGF. When injected into mice bearing subcutaneously implanted human malignant glioma, EPCs specifically accumulated at the sites of tumors and differentiated into mature endothelial cells (ECs), which accounted for 18% ECs of the tumor microvessels. The incorporation of circulating EPCs into tumor vessel walls significantly affected the morphology and structure of the vasculature. Our results suggest that circulating EPCs constitute important components of tumor microvessel network and contribute to tumor microvascular architecture phenotype heterogeneity.

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Acknowledgements

We thank Mrs Wei Sun and Miss Li-Ting Wang (Central Laboratory, Third Military Medical University, Chongqing, China) for their technical assistance in laser confocal scanning microscopy. This study was supported by grants from the National Basic Research Program of China (973 Program, No. 2006CB708503) and the Outstanding Scholar Fellowship of P.L.A. (No.06J012).

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Authors and Affiliations

  1. Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China

    Hua-rong Zhang, Fei-lan Chen, Chen-ping Xu, Yi-fang Ping, Qing-liang Wang & Xiu-wu Bian

  2. Department of Obstetrics and Gynecology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China

    Zi-qing Liang

  3. Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, 21702, USA

    Ji Ming Wang

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  1. Hua-rong Zhang
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Correspondence to Xiu-wu Bian.

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Hua-rong Zhang, Fei-lan Chen and Chen-ping Xu—contributed equally to this study.

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Zhang, Hr., Chen, Fl., Xu, Cp. et al. Incorporation of endothelial progenitor cells into the neovasculature of malignant glioma xenograft. J Neurooncol 93, 165–174 (2009). https://doi.org/10.1007/s11060-008-9757-4

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