Mesenchymal stem cells show little tropism for the resting and differentiated cancer stem cell-like glioma cells.
Intrinsic resistance of glioma cells to radiation and chemotherapy is currently hypothesized to be partially attributed to the existence of cancer stem cells. Emerging studies suggest that mesenchymal stem cells may serve as a potential carrier for delivery of therapeutic genes to disseminated glioma cells. However, the tropism character of mesenchymal stem cells for cancer stem cell-like glioma cells has rarely been described. In this study, we obtained homologous bone marrow-derived (BM-) and adipose tissue-derived (AT-) mesenchymal stem cells (MSCs), fibroblast, and cancer stem cell-like glioma cells (CSGCs) from tumor-bearing mice, and compared the tropism character of BM- and AT-MSCs for CSGCs with various form of existence. To characterize the cell proliferation and differentiation, the spheroids of CSGCs were cultured on the surface of the substrate with different stiffness, combined with or withdrew basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) in medium. Our results showed that the CSGCs during the process of cell proliferation, but not in resting and differentiated status, display strong tropism characteristics on both BM- and AT-MSCs, as well as the expression of their cell chemokine factors which mediate cell migration. If the conclusion is further confirmed, it may expose a fatal flaw of MSCs as tumor-targeted delivery of therapeutic agents in the treatment of the CSGCs, even other cancer stem cells, because there always exist a part of cancer stem cells that are in resting status. Overall, our findings provide novel insight into the complex issue of the MSCs as drug delivery in the treatment of brain tumors, especially in tumor stem cells.
Department of Neurosurgery, The Fifth Central Hospital of Tianjin, Tianjin, P.R. China.
Zhenlin
Z
Liu
Department of Pathology, The Fifth Central Hospital of Tianjin, Tianjin, P.R. China.
Zhongmin
Z
Jiang
Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Jianyong
J
Huang
Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Shuqiang
S
Huang
Central Laboratory, The Fifth Central Hospital of Tianjin, Tianjin, P.R. China.
Yanxia
Y
Li
Central Laboratory, The Fifth Central Hospital of Tianjin, Tianjin, P.R. China.
Feng
F
Sheng
Department of Neurosurgery, The Fifth Central Hospital of Tianjin, Tianjin, P.R. China.
Simiao
S
Yu
Tianjin Neurological Institute, Tianjin Medical University General Hospital, Ministry of Education, Tianjin, P.R. China.
Shizhu
S
Yu
Department of Neurosurgery, The Fifth Central Hospital of Tianjin, Tianjin, P.R. China.
Xiaozhi
X
Liu
D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001932:Brain Neoplasms / Q000473:pathology*; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005910:Glioma / Q000473:pathology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D014411:Neoplastic Stem Cells / Q000166:cytology*; D011836:Radiation Tolerance; D051381:Rats; D017207:Rats, Sprague-Dawley; D018874:Spheroids, Cellular; D019089:Stem Cell Factor / Q000378:metabolism; D018523:Tropism; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12; D019089:Stem Cell Factor; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat