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Dual Effects of Melanoma Cell-derived Factors on Bone Marrow Adipocytes Differentiation
Published on: August 23, 2018
Mesenchymal stem cell-derived interleukin-28 drives the selection of apoptosis resistant bone metastatic prostate
Jeremy J McGuire1,2, Jeremy S Frieling2, Chen Hao Lo1,2
1Cancer Biology Ph.D. Program, University of South Florida, Tampa, FL, USA.
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.
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