Targeting cellular heterogeneity with CXCR2 blockade for the treatment of therapy-resistant prostate cancer.

ABSTRACT: Hormonal therapy targeting androgen receptor (AR) is initially effective to treat prostate cancer (PCa), but it eventually fails. It has been hypothesized that cellular heterogeneity of PCa, consisting of AR⁺ luminal tumor cells and AR^- neuroendocrine (NE) tumor cells, may contribute to therapy failure. Here, we describe the successful purification of NE cells from primary fresh human prostate adenocarcinoma based on the cell surface receptor C-X-C motif chemokine receptor 2 (CXCR2). Functional studies revealed CXCR2 to be a driver of the NE phenotype, including loss of AR expression, lineage plasticity, and resistance to hormonal therapy. CXCR2-driven NE cells were critical for the tumor microenvironment by providing a survival niche for the AR⁺ luminal ce

SUBMITTER: Li Y 

PROVIDER: S-EPMC7238624 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature