Department of Biotechnology Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy.
Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
Int J Mol Sci. 2020 Jul 23;21(15):5207. doi: 10.3390/ijms21155207.
Osteosarcomas (OSs) are bone tumors most commonly found in pediatric and adolescent patients characterized by high risk of metastatic progression and recurrence after therapy. Effective therapeutic management of this disease still remains elusive as evidenced by poor patient survival rates. To achieve a more effective therapeutic management regimen, and hence patient survival, there is a need to identify more focused targeted therapies for OSs treatment in the clinical setting. The role of the OS tumor stroma microenvironment plays a significant part in the development and dissemination of this disease. Important components, and hence potential targets for treatment, are the tumor-infiltrating macrophages that are known to orchestrate many aspects of OS stromal signaling and disease progression. In particular, increased infiltration of M2-like tumor-associated macrophages (TAMs) has been associated with OS metastasis and poor patient prognosis despite currently used aggressive therapies regimens. This review aims to provide a summary update of current macrophage-centered knowledge and to discuss the possible roles that macrophages play in the process of OS metastasis development focusing on the potential influence of stromal cross-talk signaling between TAMs, cancer-stem cells and additional OSs tumoral microenvironment factors.
骨肉瘤（OSs）是最常见于儿科和青少年患者的骨肿瘤，其特征是治疗后转移进展和复发的风险高。尽管患者的生存率仍然很差，但这种疾病的有效治疗管理仍然难以实现。为了实现更有效的治疗管理方案，从而提高患者的生存率，需要在临床环境中为 OS 治疗确定更有针对性的靶向治疗方法。OS 肿瘤基质微环境的作用在疾病的发展和传播中起着重要作用。重要的组成部分，也是治疗的潜在靶点，是浸润肿瘤的巨噬细胞，已知其可以协调 OS 基质信号和疾病进展的许多方面。特别是，尽管目前使用了积极的治疗方案，但 M2 样肿瘤相关巨噬细胞（TAMs）的浸润增加与 OS 转移和患者预后不良有关。本综述旨在提供当前以巨噬细胞为中心的知识的最新总结，并讨论巨噬细胞在 OS 转移发展过程中可能发挥的作用，重点关注 TAMs、癌症干细胞和其他 OS 肿瘤微环境因素之间基质交叉对话信号的潜在影响。
