ABSTRACT
@#[Abstract] Objective: To study the effect and possible mechanism of TGF-β2 on the invasion of glioma stem cells (GSCs). Methods: Tumor tissues of 8 patients with glioblastoma multiforme, who underwent resection at Department of Neurosurgery of the FirstAffiliated Hospital of China Medical University duringApril 2016 toApril 2017, were collected. The primary culture of glioma cells were conducted with trypsin digestion. Partial primary glioma cells were seeded into serum-free DMEM/F12 culture medium containing EGF, bFGF and B27 to obtain suspension of tumor spheres. Immunoflurenscent staining and differentiation assay were used to detect whether the tumor spheres were GSCs. TGF-β2 secretion ability of GSCs was determined by ELISAassay.After transfection of TGF-β2 siRNA, the invasion ability of glioma stem cells was determined by Transwell assay. Western blotting was used to examine the effect of TGF-β2 on expression of matrix metalloproteinases (MMP) in glioma stem cells. Results: The suspended tumor spheres were proved to be GSCs by immunofluorescent staining and differentiation assay; the tumor spheres expressed the marker of GSCs（CD133）and had the ability to multi-differentiate (glia and neuronal cells). Compared with the primary glioma cells, Glioma stem cells exerted significantly improved TGF-β2 secretion ability ([74.13±3.63] vs [46.13±2.61] pg/ml, P<0.05); and TGF-β2 silencing significantly reduced the invasion ability of glioma stem cells ([105.71±8.69] vs [63.67±5.93], P<0.05) and inhibited MMP-2 and MMP-9 expressions. Conclusion: TGF-β2 can promote the invasiveness of glioma stem cells through MMP-2 and MMP-9 pathway.
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@#[Abstract] Objective: To detect the expression of zinc transporter 1 (ZnT1) gene in glioma tissue, and to explore its effect on the proliferation, migration and invasion of U87 cells. Methods: From October 2015 to January 2017, 20 patients with glioma, who received no chemoradiotherapy before operation, were collected from Department of Neurosurgery, the First Affiliated Hospital of China Medical University. The protein and mRNA content of ZnT1 in glioma tissues and adjacent tissues were detected by Western blotting and Realtime PCR, respectively. ZnT1 and si-ZnT1 plasmids were transfected into glioma U87 cell line respectively to construct ZnT1 over-expression U87 cell line and ZnT1 knockdown U87 cell line. The effects of ZnT1 on proliferation, migration and invasion of U87 cells were detected by MTT and transwell assay. Results: Both mRNA and protein expressions of ZnT1 in glioma tissues was significantly higher than those in adjacent tissues (all P<0.05). U87 cell lines with ZnT1 over-expression and knockdown were successfully constructed. Compared with the control group and empty plasmid control group, the proliferation (0.54±0.01 vs 0.45±0.04, 0.43±0.03, P<0.01), invasion and migration (all P<0.05) of U87 cells with ZnT1 over-expression were significantly increased at 12 h after transfection; however, the proliferation (0.37±0.03 vs 0.45±0.01, 0.44±0.03, P<0.01), invasion and migration (all P<0.05) of U87 cells with ZnT1 knockdown were decreased significantly. Conclusion: ZnT1 was highly expressed in glioma tissues, and promoted the proliferation, migration and invasion of glioma U87 cells.
ABSTRACT
@#[Abstract] Glioblastoma multiforme (GBM) is the most common malignant tumor of the central nervous system. Despite advances in traditional treatment strategies that combine surgery with radiotherapy and chemotherapy, GBM remains one of the most lethal diseases with dismal prognosis. Epithelial-interstitial transformation (EMT) is an important biological process for the invasion and migration of malignant tumors derived from epithelial cells, which is closely related to the pathological behaviors of GBM including invasion, migration, resistance to chemotherapy and radiotherapy. This review will introduce the concept of EMT and its pathophysiological process, especially the latest findings related to the GBM biology. Besides, gene regulation and signaling pathways of EMT (such as matrix metalloproteinases [MMP], TGF-β, transcription factors Snail and Twist etc.) participated in GBM are also introduced, thereby providing a new insight into the fundamental researches and clinical treatments of GBM.