Tan Yuying, Zhao Lei, Yang Yong-Guang, Liu Wentao
Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, China.
National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, Jilin University, Changchun, China.
Front Oncol. 2022 Jul 8;12:953283. doi: 10.3389/fonc.2022.953283. eCollection 2022.
Osteopontin (OPN) is a multifunctional phosphorylated protein. It is widely involved in solid tumor progression, such as intensification of macrophage recruitment, inhibition of T-cell activity, aggravation of tumor interstitial fibrosis, promotion of tumor metastasis, chemotherapy resistance, and angiogenesis. Most of these pathologies are affected by tumor-associated macrophages (TAMs), an important component of the tumor microenvironment (TME). TAMs have been extensively characterized, including their subsets, phenotypes, activation status, and functions, and are considered a promising therapeutic target for cancer treatment. This review focuses on the interaction between OPN and TAMs in mediating tumor progression. We discuss the strategies for targeting OPN and TAMs to treat cancer and factors that may affect the therapeutic outcomes of blocking OPN or depleting TAMs. We also discuss the role of cancer cell- vs. TAM-derived OPN in tumorigenesis, the mechanisms of how OPN affects TAM recruitment and polarization, and why OPN could mediate anti-tumor and pro-tumor effects, as well as previously reported discrepancies.
骨桥蛋白（OPN）是一种多功能磷酸化蛋白。它广泛参与实体瘤进展，如增强巨噬细胞募集、抑制T细胞活性、加剧肿瘤间质纤维化、促进肿瘤转移、化疗耐药及血管生成。这些病理过程大多受肿瘤相关巨噬细胞（TAM）影响，TAM是肿瘤微环境（TME）的重要组成部分。TAM已得到广泛研究，包括其亚群、表型、激活状态和功能，被认为是癌症治疗中一个有前景的治疗靶点。本综述聚焦于OPN与TAM在介导肿瘤进展中的相互作用。我们讨论了靶向OPN和TAM治疗癌症的策略以及可能影响阻断OPN或清除TAM治疗效果的因素。我们还讨论了癌细胞源性与TAM源性OPN在肿瘤发生中的作用、OPN影响TAM募集和极化的机制、OPN为何能介导抗肿瘤和促肿瘤作用以及先前报道的差异。
