The prognostic implications of macrophage polarization in advanced and therapy-resistant prostate cancer

Abstract Tumor-associated macrophages (TAMs) are components of the spatial microenvironment many solid neoplasms. In prostate cancer (PCa), TAMs linked to a poor prognosis. PCa is characterized by enhanced tumor lipid production and TAM accumulation. However, interplay between lipid-producing cells uptake has yet be determined. Human tissue microarrays were evaluated for (CD68+) M2/M1 (CD206+/CD86+) levels correlated with aggressiveness multiplex immunohistochemistry. Standard 22rv1, PC3 DU145 used develop chemoresistant sublines which validated using dose-response viability assays immunoblotting resistance-associated markers enzymes. Cancer cell-derived extracellular vesicles (EVs) isolated from cell culture supernatants size exclusion chromatography incubated U937-derived macrophages, followed flow cytometric evaluation M1 M2 markers. Proteomic human tumors indicates that CD68+ correlate aggressive, metastatic PCa. Furthermore, higher M2-to-M1 ratio also correlates disease compared normal or localized tumors. Chemoresistant exhibited an lipogenic phenotype naive over-production lipids was EV-mediated reprogramming toward M2-like phenotype. These findings indicate alternative activation therapy resistant Moreover, our data suggest metabolism may influence tumor-associated macrophage function through intercellular signaling. Puerto Rico Science Research Technology Trust