Xiao Qiang, Zhang Xuepu, Wu Yuexin, Yang Yu
The Department of Hand and Foot Surgery, The First Affiliated Hospital of Liaoning Medical University, 2 Renmin Road, Guta District, Jinzhou, 121001, China,
Tumour Biol. 2014 Aug;35(8):7611-6. doi: 10.1007/s13277-014-2005-y. Epub 2014 May 6.
Osteosarcoma is the most malignant bone tumor characterized by high local aggressiveness and poor therapeutic outcome. Tumor-associated macrophages (TAM) have been shown to participate in the development and progress of many types of cancer cells. However, whether TAM may play a role in the pathogenesis of osteosarcoma is largely unknown. In a mouse model of human osteosarcoma implantation, we showed that the recruited macrophages at the site of the implanted tumor were polarized to an M2 subtype (same as TAM) during the development and growth of the osteosarcoma. In a loss-of-function experiment, we deleted these TAM with a specific macrophage-eliminating liposome, which resulted in decreased tumor growth. Moreover, when the epidermal growth factor receptor (EGFR) in the implanted cancer cells was inhibited by shRNA, the tumor failed to grow in response to the recruited macrophages. Taken together, for the first time, we show that the growth of an osteosarcoma is EGFR signaling-dependent and TAM-mediated. Our data suggest that TAM and EGFR may be good targets for treating human osteosarcoma.
骨肉瘤是最具恶性的骨肿瘤，其特点是局部侵袭性强且治疗效果差。肿瘤相关巨噬细胞（TAM）已被证明参与多种癌细胞的发生和发展。然而，TAM是否在骨肉瘤的发病机制中起作用在很大程度上尚不清楚。在人骨肉瘤植入的小鼠模型中，我们发现植入肿瘤部位募集的巨噬细胞在骨肉瘤的发生和生长过程中极化成为M2亚型（与TAM相同）。在功能缺失实验中，我们用特异性巨噬细胞清除脂质体清除这些TAM，这导致肿瘤生长减缓。此外，当植入癌细胞中的表皮生长因子受体（EGFR）被shRNA抑制时，肿瘤对募集的巨噬细胞无生长反应。综上所述，我们首次表明骨肉瘤的生长是EGFR信号依赖且由TAM介导的。我们的数据表明，TAM和EGFR可能是治疗人类骨肉瘤的良好靶点。
