Circulating endothelial progenitor cells are involved in VEGFR-2-related endothelial differentiation in glioma

Wang,Le; Chen,Lu; Wang,Qianfeng; Wang,Lijuan; Wang,Haibao; Shen,Yujun; Li,Xiaohu; Fu,Yu; Shen,Yuxian; Yu,Yongqiang

doi:10.3892/or.2014.3467

Circulating endothelial progenitor cells are involved in VEGFR-2-related endothelial differentiation in glioma

Authors:
- Le Wang
- Lu Chen
- Qianfeng Wang
- Lijuan Wang
- Haibao Wang
- Yujun Shen
- Xiaohu Li
- Yu Fu
- Yuxian Shen
- Yongqiang Yu
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Affiliations: Department of Radiology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230022, P.R. China, Biopharmaceutical Research Institute, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, P.R. China
Published online on: September 5, 2014 https://doi.org/10.3892/or.2014.3467
Pages: 2007-2014

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Abstract

Endothelial progenitor cells (EPCs) play important roles in maintaining endothelial integrity and tumor vascularization. However, the differentiation of EPCs in the neoangiogenesis of gliomas has not yet been fully elucidated. The purpose in this study was to investigate the profile of EPC differentiation in rat C6 glioma using magnetic resonance imaging (MRI), a non-invasive monitoring assay. To achieve this goal, we isolated EPCs from rat bone marrow and identified them by detecting CD34, CD133, and VEGFR-2, the markers of EPCs. Coexpression of Ac-LDL and UEA-1 in EPCs was also determined. To dynamically monitor the migration of circulating cells, the EPCs were labeled with ultrasmall superparamagnetic iron oxide (USPIO) and injected by tail vein into rats bearing C6 glioma. MRI was performed at 24, 48, and 96 h after injection. The distribution and differentiation of EPCs were confirmed by histology. We found that the USPIO-labeled EPCs appeared at the tumor periphery where a large number of CD105-positive cells appeared at 24 h after injection by using MRI scanning. Ninety-six hours after injection, immunohistochemistry and Prussian blue staining were used to observe the labeled EPCs in the tumor tissue. We found that many of the labeled EPCs were overlapped with VEGFR-2-positive endothelial cells, but not CD105- or CD34-positive cells. These results suggest that EPCs can cross the blood-brain barrier from peripheral blood and home to tumors, where they differentiate into endothelial cells, including VEGFR-2-positive endothelial cells. MRI is a useful method for dynamically tracking the migration of USPIO-labeled EPCs.

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1	Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G and Isner JM: Isolation of putative progenitor endothelial cells for angiogenesis. Science. 275:964–967. 1997. View Article : Google Scholar : PubMed/NCBI
2	Reyes M, Dudek A, Jahagirdar B, Koodie L, Marker PH and Verfaillie CM: Origin of endothelial progenitors in human postnatal bone marrow. J Clin Invest. 109:337–346. 2002. View Article : Google Scholar : PubMed/NCBI
3	Eggermann J, Kliche S, Jarmy G, Hoffmann K, Mayr-Beyrle U, Debatin KM, Waltenberger J and Beltinger C: Endothelial progenitor cell culture and differentiation in vitro: a methodological comparison using human umbilical cord blood. Cardiovasc Res. 58:478–486. 2003. View Article : Google Scholar : PubMed/NCBI
4	Fan CL, Li Y, Gao PJ, Liu JJ, Zhang XJ and Zhu DL: Differentiation of endothelial progenitor cells from human umbilical cord blood CD 34⁺ cells in vitro. Acta Pharmacol Sin. 24:212–218. 2003.PubMed/NCBI
5	Wu KH, Zhou B, Lu SH, Feng B, Yang SG, Du WT, Gu DS, Han ZC and Liu YL: In vitro and in vivo differentiation of human umbilical cord derived stem cells into endothelial cells. J Cell Biochem. 100:608–616. 2007. View Article : Google Scholar : PubMed/NCBI
6	Muta M, Matsumoto G, Hiruma K, Saji S, Nakashima E and Toi M: Impact of vasculogenesis on solid tumor growth in a rat model. Oncol Rep. 10:1213–1218. 2003.PubMed/NCBI
7	Sho E, Sho M, Nanjo H, Kawamura K, Masuda H and Dalman RL: Hemodynamic regulation of CD34⁺ cell localization and differentiation in experimental aneurysms. Arterioscler Thromb Vasc Biol. 24:1916–1921. 2004.PubMed/NCBI
8	Anderson SA, Glod J, Arbad AS, Noel M, Ashari P, Fine HA and Frank JA: Noninvasive MR imaging magnetically labeled stem cells to directly identify neovasculature in a glioma model. Blood. 105:420–425. 2005. View Article : Google Scholar : PubMed/NCBI
9	Arbab AS, Pandit SD, Anderson SA, Yocum GT, Bur M, Frenkel V, Khuu HM, Read EJ and Frank JA: Magnetic resonance imaging and confocal microscopy studies of magnetically labeled endothelial progenitor cells trafficking to sites of tumor angiogenesis. Stem Cells. 24:671–678. 2006. View Article : Google Scholar
10	Wassmann S, Werner N, Czech T and Nickenig G: Improvement of endothelial function by systemic transfusion of vascular progenitor cells. Circ Res. 99:e74–e83. 2006. View Article : Google Scholar : PubMed/NCBI
11	Laing AJ, Dillon JP, Condon ET, Street JT, Wang JH, McGuinness AJ and Redmond HP: Mobilization of endothelial precursor cells: systemic vascular response to musculoskeletal trauma. J Orthop Res. 25:44–50. 2007. View Article : Google Scholar : PubMed/NCBI
12	Szmitko PE, Fedak PW, Weisel RD, Stewart DJ, Kutryk MJ and Verma S: Endothelial progenitor cells: new hope for a broken heart. Circulation. 107:3093–3100. 2003. View Article : Google Scholar : PubMed/NCBI
13	Lyden D, Hattori K, Dias S, Costa C, Blaikie P, et al: Impaired recruitment of bone-marrow derived endothelial and haematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med. 7:1194–1201. 2001. View Article : Google Scholar : PubMed/NCBI
14	Rafii S, Lyden D, Benezra R, Hattori K and Heissig B: Vascular and haematopoietic stem cells: Novel targets for anti-angiogenesis therapy? Nat Rev Cancer. 2:826–835. 2002. View Article : Google Scholar : PubMed/NCBI
15	Rafat N, Beck GCh, Schulte J, Tuettenberg J and Vajkoczy P: Circulating endothelial progenitor cells in malignant gliomas. J Neurosurg. 112:43–49. 2010. View Article : Google Scholar : PubMed/NCBI
16	Varma NR, Janic B, Iskander AS, Shankar A, Bhuiyan MP, Soltanian-Zadeh H, Jiang Q, Barton K, Ali MM and Arbab AS: Endothelial progenitor cells (EPCs) as gene carrier system for rat model of human glioma. PLoS One. 7:e303102012. View Article : Google Scholar : PubMed/NCBI
17	Corsini E, Ciusani E, Gaviani P, Silvani A, Canazza A, Bernardi G, Calatozzolo C, DiMeco F and Salmaggi A: Decrease in circulating endothelial progenitor cells in treated glioma patients. J Neurooncol. 108:123–129. 2012. View Article : Google Scholar : PubMed/NCBI
18	Soda Y, Marumoto T, Friedmann-Morvinski D, Soda M, Liu F, Michiue H, Pastorino S, Yang M, Hoffman RM, Kesari S and Verma IM: Transdifferentiation of glioblastoma cells into vascular endothelial cells. Proc Natl Acad Sci USA. 108:4274–4280. 2011. View Article : Google Scholar : PubMed/NCBI
19	Neri M, Maderna C, Cavazzin C, Deidda-Vigoriti V, Politi LS, Scotti G, Marzola P, Sbarbati A, Vescovi AL and Gritti A: Efficient in vitro labeling of human neural precursor cells with superparamagnetic iron oxide particles: relevance for in vivo cell tracking. Stem Cells. 26:505–516. 2008. View Article : Google Scholar : PubMed/NCBI
20	Hristov M, Erl W and Weber PC: Endothelial progenitor cells: isolation and characterization. Trends Cardiovasc Med. 13:201–206. 2003. View Article : Google Scholar : PubMed/NCBI
21	Yoder MC, Mead LE, Prater D, Krier TR, Mroueh KN, Li F, Krasich R, Temm CJ, Prchal JT and Ingram DA: Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood. 109:1801–1809. 2007. View Article : Google Scholar : PubMed/NCBI
22	Arbab AS, Janic B, Knight RA, Anderson SA, Pawelczyk E, Rad AM, Read EJ, Pandit SD and Frank JA: Detection of migration of locally implanted AC133⁺ stem cells by cellular magnetic resonance imaging with histological findings. FASEB J. 22:3234–3246. 2008.PubMed/NCBI
23	Povsic TJ, Zavodni KL, Vainorius E, Kherani JF, Goldschmidt-Clermont PJ and Peterson ED: Common endothelial progenitor cell assays identify discrete endothelial progenitor cell populations. Am Heart J. 157:335–344. 2009. View Article : Google Scholar : PubMed/NCBI
24	Li C, Guo B, Wilson PB, Stewart A, Byrne G, Bundred N and Kumar S: Plasma levels of soluble CD105 correlate with metastasis in patients with breast cancer. Int J Cancer. 89:122–126. 2000. View Article : Google Scholar : PubMed/NCBI
25	Zheng PP, van der Weiden M, van der Spek PJ, Vincent AJ and Kros JM: Intratumoral, not circulating, endothelial progenitor cells share genetic aberrations with glial tumor cells. J Cell Physiol. 228:1383–1390. 2013. View Article : Google Scholar : PubMed/NCBI
26	Janic B, Jafari-Khouzani K, Babajani-Feremi A, Iskander AS, Varma NR, Ali MM, Knight RA and Arbab AS: MRI tracking of FePro labeled fresh and cryopreserved long term in vitro expanded human cord blood AC133⁺ endothelial progenitor cells in rat glioma. PLoS One. 7:e375772012. View Article : Google Scholar : PubMed/NCBI
27	Chaumeil MM, Gini B, Yang H, Iwanami A, Sukumar S, Ozawa T, Pieper RO, Mischel PS, James CD, Berger MS and Ronen SM: Longitudinal evaluation of MPIO-labeled stem cell biodistribution in glioblastoma using high resolution and contrast-enhanced MR imaging at 14.1 Tesla. Neuro Oncol. 14:1050–1061. 2012. View Article : Google Scholar : PubMed/NCBI
28	Varma NR, Shankar A, Iskander A, Janic B, Borin TF, Ali MM and Arbab AS: Differential biodistribution of intravenously administered endothelial progenitor and cytotoxic T-cells in rat bearing orthotopic human glioma. BMC Med Imaging. 13:172013. View Article : Google Scholar