Exosomes derived from ovarian cancer promote the progression of ovarian cancer through macrophage M2 polarization mediated by the THBS1/TGFBI signaling axis
Tumor-derived exosomes play a critical role in facilitating intercellular communication between cancer cells and tumor-associated macrophages (TAMs). Nevertheless, the precise molecular mechanisms underlying exosome-mediated interactions specifically in ovarian cancer remain incompletely elucidated. TAMs were treated with exosomes isolated from clinical ovarian cancer specimens. Macrophage polarization was assessed using qRT-PCR, and western blot analysis. RNA sequencing was employed to identify key genes within the exosomes. The malignant phenotype of ovarian cancer cells was evaluated through cell counting kit-8 (CCK-8), Transwell assay, and wound-healing assays. Our findings showed that exosomes derived from both early and late-stage malignant ovarian cancer tissues induced the upregulation of all M2 macrophage markers and the downregulation of M1 markers. RNA sequencing analysis identified thrombospondin-1 (THBS1) as a potential pivotal gene influencing exosome-regulated TAM polarization. THBS1 knockdown within exosomes inhibited the polarization of TAMs toward the M2 phenotype and concurrently decreased transforming growth factor beta induced (TGFBI) expression in macrophages. Notably, TGFBI knockdown in TAM reversed the M2 polarization induced by ovarian cancer cells-derived exosomes. In vivo, ovarian cancer cell-derived exosomes facilitate cancer progression, concomitantly increasing the polarization of M2 macrophages and upregulating THBS1 and TGFBI expression within tumor tissues. THBS1, carried by ovarian cancer-derived exosomes, promotes M2 polarization of TAMs by modulating TGFBI expression. The subsequent M2 polarization of TAMs contributes to the establishment of an immunosuppressive tumor microenvironment, thereby facilitating disease progression. Consequently, targeting the exosome-mediated signaling axis between cancer cells and macrophages represents a promising avenue for developing novel therapeutic interventions.