Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Department of Orthopedics, Shanghai Jingan Zhaibei Hospital, Shanghai 200070, China.
J Biochem. 2020 Sep 1;168(3):265-271. doi: 10.1093/jb/mvaa044.
As a research hotspot in recent years, bone mesenchymal stem cells (BMSCs) play an important role in the process of a variety of human diseases, including cancers. However, in osteosarcoma, the role of BMSCs and their communication with tumour cells are not clear. In this study, we validated the communication of osteosarcoma (OS) cells with BMSCs. The results showed that the conditioned medium of osteosarcoma cell line U2OS (U2OS-CM) induces the carcinoma-associated fibroblasts (CAFs)-like transformation of BMSCs and promotes the proliferation, migration and invasion of BMSCs. Mechanistically, treatment of human bone mesenchymal stem cells (hBMSCs) with U2OS-CM results in a significant increase in the IL-6 expression and phosphorylation of STAT3. Furthermore, blockade of the IL-6/STAT3 signalling in hBMSCs rescues the transformation of CAF phenotype induced by U2OS-CM. And, human IL-6 can directly increase the expression of the CAF marker genes in hMSCs. Meanwhile, IL-6/STAT3 signalling involves in promoting effects of U2OS-CM on the proliferation, migration and invasion of BMSCs. In summary, our results suggest that BMSCs communicate with OS cells through IL-6/STAT3 signalling and play an important role in the progress of osteosarcoma.
作为近年来的研究热点，骨间充质干细胞（BMSCs）在包括癌症在内的多种人类疾病的发生过程中发挥着重要作用。然而，在骨肉瘤中，BMSCs 的作用及其与肿瘤细胞的通讯尚不清楚。在本研究中，我们验证了骨肉瘤（OS）细胞与 BMSCs 的通讯。结果表明，骨肉瘤细胞系 U2OS 的条件培养基（U2OS-CM）诱导 BMSCs 的癌相关成纤维细胞（CAFs）样转化，并促进 BMSCs 的增殖、迁移和侵袭。在机制上，U2OS-CM 处理人骨髓间充质干细胞（hBMSCs）会导致 IL-6 表达和 STAT3 磷酸化显著增加。此外，阻断 hBMSCs 中的 IL-6/STAT3 信号通路可挽救 U2OS-CM 诱导的 CAF 表型转化。并且，人 IL-6 可直接增加 hMSCs 中 CAF 标记基因的表达。同时，IL-6/STAT3 信号通路涉及促进 U2OS-CM 对 BMSCs 增殖、迁移和侵袭的作用。总之，我们的研究结果表明，BMSCs 通过 IL-6/STAT3 信号通路与 OS 细胞通讯，并在骨肉瘤的进展中发挥重要作用。
