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Increased in vivo angiogenic effect of glioma stromal mesenchymal stem-like cells on glioma cancer stem cells from patients with glioblastoma

Authors
 Byung Ho Kong  ;  Hyun-Do Shin  ;  Se-Hoon Kim  ;  Hyun-Su Mok  ;  Jin-Kyoung Shim  ;  Ji-Hyun Lee  ;  Hye-Jin Shin  ;  Yong-Min Huh  ;  Eui-Hyun Kim  ;  Eun-Kyung Park  ;  Jong Hee Chang  ;  Dong-Seok Kim  ;  Yong-Kil Hong  ;  Sun Ho Kim  ;  Su-Jae Lee  ;  Seok-Gu Kang 
Citation
 INTERNATIONAL JOURNAL OF ONCOLOGY, Vol.42(5) : 1754-1762, 2013 
Journal Title
 INTERNATIONAL JOURNAL OF ONCOLOGY 
ISSN
 1019-6439 
Issue Date
2013
MeSH
Animals ; Apoptosis ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Coculture Techniques ; Female ; Glioblastoma/metabolism ; Glioblastoma/pathology ; Glioma/genetics ; Glioma/pathology* ; Humans ; Male ; Mesenchymal Stromal Cells/metabolism ; Mesenchymal Stromal Cells/pathology* ; Mice ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology* ; Neovascularization, Pathologic/metabolism* ; Stromal Cells/cytology ; Stromal Cells/metabolism ; Xenograft Model Antitumor Assays
Keywords
Animals ; Apoptosis ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Coculture Techniques ; Female ; Glioblastoma/metabolism ; Glioblastoma/pathology ; Glioma/genetics ; Glioma/pathology* ; Humans ; Male ; Mesenchymal Stromal Cells/metabolism ; Mesenchymal Stromal Cells/pathology* ; Mice ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology* ; Neovascularization, Pathologic/metabolism* ; Stromal Cells/cytology ; Stromal Cells/metabolism ; Xenograft Model Antitumor Assays
Abstract
The presence of glioma stromal mesenchymal stem‑like cells (GS-MSLCs) in tumors from glioma patients has been previously reported. The mechanisms through which these cells function as a part of the glioma microenvironment, however, remain incompletely understood. We investigated the biological effects of GS-MSLCs on glioma cancer stem cells (gCSCs), testing the hypothesis that GS-MSLCs alter the biological characteristics of gCSCs. GS-MSLCs and gCSCs were isolated from different glioblastoma (GBM) specimens obtained from patients. In in vitro experiments, gCSCs were cultured alone or co-cultured with GS-MSLCs, and gCSCs cell counts were compared between the two groups. In addition, two groups of orthotopic GBM xenografts in mice were created, one using gCSCs from the monoculture group and one using gCSCs isolated from the co-culture group, and tumor volume and survival were analyzed. Furthermore, in vivo proliferation, apoptosis and vessel formation were examined using immunohistochemical analyses. In vitro cell counts for gCSCs co-cultured with GS-MSLCs increased 3-fold compared to gCSCs cultured alone. In orthotopic xenograft experiments, mice injected with gCSCs isolated from the co-culture group had significantly larger tumor volume, measured on day 40 after injection, and their survival times were shorter. Immunohistochemical analysis showed increased tumor expression of CD31, indicative of enhanced microvessel formation in mice injected with gCSCs co-cultured with GS-MSLCs compared to mice injected with gCSCs cultured alone. However, proliferation (PCNA) and apoptosis (TUNEL) markers showed no significant difference between the two groups. In conclusion, GS-MSLCs may influence the biological properties of gCSCs, shifting them towards a more aggressive status; moreover, increased angiogenesis may be a critical component of this mechanism.
Full Text
http://www.spandidos-publications.com/ijo/42/5/1754
DOI
10.3892/ijo.2013.1856
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kang, Seok Gu(강석구) ORCID logo https://orcid.org/0000-0001-5676-2037
Kim, Dong Seok(김동석)
Kim, Sun Ho(김선호) ORCID logo https://orcid.org/0000-0003-0970-3848
Kim, Se Hoon(김세훈) ORCID logo https://orcid.org/0000-0001-7516-7372
Kim, Eui Hyun(김의현) ORCID logo https://orcid.org/0000-0002-2523-7122
Park, Eun Kyung(박은경)
Lee, Ji Hyun(이지현) ORCID logo https://orcid.org/0000-0002-9223-9478
Chang, Jong Hee(장종희)
Huh, Yong Min(허용민) ORCID logo https://orcid.org/0000-0002-9831-4475
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/86559
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