Interleukin-6 induces malignant transformation of rat mesenchymal stem cells in association with enhanced signaling of signal transducer and activator of transcription 3.
Bottom Line: The expression of IL-6 was significantly increased in MSCs cocultured with glioma cells, which was associated with significantly increased expressions of soluble IL-6 receptor, transmembrane glycoprotein GP130, STAT3, phosphorylated STAT3, CyclinD1, and Bcl-xl.Similar results were obtained when the MSCs were treated with IL-6.These data suggest that IL-6 plays a critical role in malignant transformation of rat MSCs, which is associated with an enhancement of the STAT3 signaling pathway in the tumor microenvironment.
Affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.Show MeSH
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Mentions: In order to determine the tumorigenicity of the cells after malignant transformation, the MSCs cocultured with C6 glioma cells or with normal cells were injected into nude mice. Thirty days after the injection, the injected MSCs cocultured with C6 glioma cells or glioma cells themselves developed into an invasive tumor that was composed of undifferentiated cells and infiltrated to the peripheral musculus, as examined by H&E staining (Fig.3a). After the injection, the volume of invasive tumors in nude mice for each group was measured every day by rule, as shown in Figure3(b). Tumor growth and progression were similar for cells cocultured with C6 glioma cells, and glioma cells alone. The invasive tumors in the two groups grew much faster than in the normal group, further suggesting the malignant nature of the cells after coculture with C6 glioma cells. No tumor growth was observed after injection of normal MSCs or MSCs cocultured with normal astrocytes.
Affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.