Isolation and characterization of stem cell-like precursor cells from primary human anaplastic oligoastrocytoma.
A small population of stem cell-like precursors in solid tumors are linked to histological composition, progression, angiogenesis, metastasis, recurrence and drug resistance of a variety of malignant tumors. Oligoastrocytoma is the most common brain mixed glioma composed of mixed cells of oligodendroglial and astrocytic phenotypes. Identification and characterization of stem cell-like precursors in oligoastrocytoma may shed light on the oncogenesis of this unique type of tumor and assist in the design of novel therapeutic strategy. Here, tumor stem cell-like precursors were identified from primary human anaplastic oligoastrocytomas by labeling of the tumor sections with nestin and CD133. Tumor cells were cultured in vitro in stem cell medium with growth factors and the capacity of the surviving stem cell-like precursors to form tumor spheres was tested. The tumor spheres were further injected subcutaneously into nude mice to observe the contribution of stem cell-like precursors to histological composition and tumor progression. We found that primary human oligoastrocytoma tissues contained nestin+/CD133+ stem cell-like precursors. These cells differentiated into tumor cells with both oligodendroglial and astrocytic characteristics and formed tumor spheres in vitro, which upon implantation in nude mice, grew into tumor nodules containing nestin+/CD133+ cells at levels higher than in the primary tumor tissues. This study revealed for the first time that anaplastic human oligoastrocytomas contained stem cell-like precursors, which exhibit neural stem cell properties with tumorigenicity. These stem cell-like precursors may be responsible for the oligodendroglial and astrocytic components of human oligoastrocytoma and should be considered as therapeutic targets.
Yi
Liang
L
Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing, China.
Zhou
Zhi-hua
ZH
Ping
Yi-fang
YF
Chen
Jian-hong
JH
Yao
Xiao-hong
XH
Feng
Hua
H
Lu
Jia-you
JY
Wang
Ji Ming
JM
Bian
Xiu-wu
XW
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001254:Astrocytoma / Q000737:chemistry / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000737:chemistry / Q000473:pathology*; D019084:Fluorescent Antibody Technique, Indirect; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007381:Intermediate Filament Proteins / Q000032:analysis; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000032:analysis; D064231:Nestin; D010455:Peptides / Q000032:analysis; D018874:Spheroids, Cellular / Q000737:chemistry / Q000473:pathology; D014407:Tumor Cells, Cultured
D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse