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.

中文翻译：

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骨肉瘤细胞系U2OS的条件培养基可通过激活IL-6 / STAT3信号来诱导hBMSC表现出与癌相关的成纤维细胞的特征。

作为近年来的研究热点，骨髓间充质干细胞（BMSCs）在包括癌症在内的多种人类疾病的过程中发挥着重要作用。然而，在骨肉瘤中，BMSC的作用及其与肿瘤细胞的通讯尚不清楚。在这项研究中，我们验证了骨肉瘤（OS）细胞与BMSC的通信。结果表明，骨肉瘤细胞系U2OS（U2OS-CM）的条件培养基可诱导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。从机制上讲，用U2OS-CM处理人骨间充质干细胞（hBMSC）会导致IL-6表达和STAT3磷酸化显着增加。此外，对hBMSCs中IL-6 / STAT3信号的阻断可拯救U2OS-CM诱导的CAF表型转化。并且，人IL-6可以直接增加hMSC中CAF标记基因的表达。同时，IL-6 / STAT3信号传导参与促进U2OS-CM对BMSCs增殖，迁移和侵袭的作用。总之，我们的结果表明BMSC通过IL-6 / STAT3信号传导与OS细胞通讯，并在骨肉瘤的进展中起重要作用。