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.