scholarly journals Abstract 1992: Mesenchymal stem cell-derived interleukin-28 can drive the selection of apoptosis resistant bone metastatic prostate cancer

Author(s):  
Jeremy J. Mcguire ◽  
Leah Cook ◽  
Jeremy Frieling ◽  
Ayaz Muhammad ◽  
Harshani Lawrence ◽  
...  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jeremy J. McGuire ◽  
Jeremy S. Frieling ◽  
Chen Hao Lo ◽  
Tao Li ◽  
Ayaz Muhammad ◽  
...  

AbstractBone 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.


2016 ◽  
Vol 22 (1) ◽  
pp. 26-35 ◽  
Author(s):  
Kristine M. Mayle ◽  
Kathryn R. Dern ◽  
Vincent K. Wong ◽  
Kevin Y. Chen ◽  
Shijun Sung ◽  
...  

Currently, there is no curative treatment for advanced metastatic prostate cancer, and options, such as chemotherapy, are often nonspecific, harming healthy cells and resulting in severe side effects. Attaching targeting ligands to agents used in anticancer therapies has been shown to improve efficacy and reduce nonspecific toxicity. Furthermore, the use of triggered therapies can enable spatial and temporal control over the treatment. Here, we combined an engineered prostate cancer–specific targeting ligand, the A11 minibody, with a novel photothermal therapy agent, polypeptide-based gold nanoshells, which generate heat in response to near-infrared light. We show that the A11 minibody strongly binds to the prostate stem cell antigen that is overexpressed on the surface of metastatic prostate cancer cells. Compared to nonconjugated gold nanoshells, our A11 minibody-conjugated gold nanoshell exhibited significant laser-induced, localized killing of prostate cancer cells in vitro. In addition, we improved upon a comprehensive heat transfer mathematical model that was previously developed by our laboratory. By relaxing some of the assumptions of our earlier model, we were able to generate more accurate predictions for this particular study. Our experimental and theoretical results demonstrate the potential of our novel minibody-conjugated gold nanoshells for metastatic prostate cancer therapy.


2018 ◽  
Vol 13 (4) ◽  
pp. 85-90 ◽  
Author(s):  
B. Ya. Alekseev ◽  
A. N. Andrianov ◽  
A. D. Kaprin

Hormone therapy of metastatic prostate cancer (mPC) has been the “golden standard” of treatment since 1941. However, survival rates in patients with this pathology have remained low. Based on the results of newer studies, early start of docetaxel chemotherapy or antiandrogen abiraterone therapy in combination with standard hormone therapy allows to significantly increase survival of patients with mPC. In this review, data from these studies and advisability of docetaxel and abiraterone at the 1st line therapy of mPC are discussed.


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