Macrophage-Derived Cholesterol Contributes to Therapeutic Resistance in Prostate Cancer.

ABSTRACT: Castration-resistant prostate cancer (CRPC) is a lethal stage of disease in which androgen receptor (AR) signaling is persistent despite androgen deprivation therapy (ADT). Most studies have focused on investigating cell-autonomous alterations in CRPC, while the contributions of the tumor microenvironment are less well understood. Here we sought to determine the role of tumor-associated macrophages in CRPC, based upon their role in cancer progression and therapeutic resistance. In a syngeneic model that reflected the mutational landscape of CRPC, macrophage depletion resulted in a reduced transcriptional signature for steroid and bile acid synthesis, indicating potential perturbation of cholesterol metabolism. As cholesterol is the precursor of the five major types of steroid hormones, we

SUBMITTER: El-Kenawi A 

PROVIDER: S-EPMC8563406 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature