| Literature DB >> 33526787 |
Jeremy J McGuire1,2, Jeremy S Frieling2, Chen Hao Lo1,2, Tao Li2, Ayaz Muhammad3, Harshani R Lawrence3, Nicholas J Lawrence3, Leah M Cook4, Conor C Lynch5.
Abstract
Bone metastatic prostate cancer (PCa) promotes mesenchymal stem cell (MSC) recruitment and their differentiation into osteoblasts. However, the effects of bone-marrow derived MSCs on PCa cells are less explored. Here, we report MSC-derived interleukin-28 (IL-28) triggers prostate cancer cell apoptosis via IL-28 receptor alpha (IL-28Rα)-STAT1 signaling. However, chronic exposure to MSCs drives the selection of prostate cancer cells that are resistant to IL-28-induced apoptosis and therapeutics such as docetaxel. Further, MSC-selected/IL-28-resistant prostate cancer cells grow at accelerated rates in bone. Acquired resistance to apoptosis is PCa cell intrinsic, and is associated with a shift in IL-28Rα signaling via STAT1 to STAT3. Notably, STAT3 ablation or inhibition impairs MSC-selected prostate cancer cell growth and survival. Thus, bone marrow MSCs drive the emergence of therapy-resistant bone metastatic prostate cancer yet this can be disabled by targeting STAT3.Entities:
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Year: 2021 PMID： 33526787 PMCID： PMC7851397 DOI： 10.1038/s41467-021-20962-6
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 17.694