Tumor-Derived Exosomal Protein Tyrosine Phosphatase Receptor Type O Polarizes Macrophage to Suppress Breast Tumor Cell Invasion and Migration.
Tumor-Derived Exosomal Protein Tyrosine Phosphatase Receptor Type O Polarizes Macrophage to Suppress Breast Tumor Cell Invasion and Migration.
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肿瘤源性外泌体蛋白O型酪氨酸磷酸酶受体极化巨噬细胞抑制乳腺肿瘤细胞侵袭和迁移
DOI：
10.3389/fcell.2021.703537
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发表时间：
2021
影响因子：
5.5
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Dong H;Xie C;Jiang Y;Li K;Lin Y;Pang X;Xiong X;Zheng J;Ke X;Chen Y;Li Y;Zhang H
肿瘤来源的外泌体含有多种核酸和蛋白质，参与肿瘤细胞与微环境之间的相互作用。然而，磷酸酶在肿瘤来源的外泌体中的功能参与尚不完全清楚。我们和其他人之前证明，O 型蛋白酪氨酸磷酸酶受体 (PTPRO) 在多种癌症类型中充当肿瘤抑制因子。此外，其在肿瘤免疫微环境中的作用仍然难以捉摸。生物信息分析显示，乳腺癌组织中PTPRO与免疫浸润密切相关，与M1样巨噬细胞呈正相关，与M2样巨噬细胞呈负相关。与过度表达 PTPRO 的乳腺癌细胞共培养会增加 M1 样肿瘤相关巨噬细胞 (TAM) 的比例，同时降低 M2 样 TAM 的比例。此外，我们观察到肿瘤来源的外泌体 PTPRO 诱导 M1 样巨噬细胞极化，并调节相应的功能表型。此外，肿瘤细胞来源的外泌体 PTPRO 抑制乳腺癌细胞侵袭和迁移，并使巨噬细胞中的 STAT 信号失活。我们的数据表明，外泌体 PTPRO 通过调节巨噬细胞极化来抑制乳腺癌侵袭和迁移。外泌体 PTPRO 的抗肿瘤作用是通过灭活巨噬细胞中的 STAT 家族介导的。这些发现强调了肿瘤源性外泌体酪氨酸磷酸酶调节肿瘤侵袭的新机制，该机制对于乳腺癌治疗策略具有转化潜力。
Tumor-derived exosomes, containing multiple nucleic acids and proteins, have been implicated to participate in the interaction between tumor cells and microenvironment. However, the functional involvement of phosphatases in tumor-derived exosomes is not fully understood. We and others previously demonstrated that protein tyrosine phosphatase receptor type O (PTPRO) acts as a tumor suppressor in multiple cancer types. In addition, its role in tumor immune microenvironment remains elusive. Bioinformatical analyses revealed that PTPRO was closely associated with immune infiltration, and positively correlated to M1-like macrophages, but negatively correlated to M2-like macrophages in breast cancer tissues. Co-cultured with PTPRO-overexpressing breast cancer cells increased the proportion of M1-like tumor-associated macrophages (TAMs) while decreased that of M2-like TAMs. Further, we observed that tumor-derived exosomal PTPRO induced M1-like macrophage polarization, and regulated the corresponding functional phenotypes. Moreover, tumor cell-derived exosomal PTPRO inhibited breast cancer cell invasion and migration, and inactivated STAT signaling in macrophages. Our data suggested that exosomal PTPRO inhibited breast cancer invasion and migration by modulating macrophage polarization. Anti-tumoral effect of exosomal PTPRO was mediated by inactivating STAT family in macrophages. These findings highlight a novel mechanism of tumor invasion regulated by tumor-derived exosomal tyrosine phosphatase, which is of translational potential for the therapeutic strategy against breast cancer.
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影响因子：
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DOI：
10.1038/nrclinonc.2016.217
发表时间：
2017-07
期刊：
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影响因子：
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作者：
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通讯作者：
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