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Stromal-AR influences the growth of epithelial cells in the development of benign prostate hyperplasia

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Abstract

Activation of epithelial-AR signaling is identified as the major cause of hyperproliferation of the cells during benign and malignant prostate conditions. However, the contribution of stromal-AR is also precarious due to its secretory actions that contribute to the progression of benign and malignant tumors. The present study was aimed to understand the influence of stromal-AR mediated actions on epithelial cells during BPH condition. The secretome (conditioned media-CM) was collected from AR agonist (testosterone-propionate-TP) and antagonist (Nilutamide-Nil) treated BPH patient-derived stromal cells and exposed to BPH epithelial cells. Epithelial cells exhibited increased cell proliferation with the treatment of CM derived from TP-treated stromal cells (TP-CM) but did not support the clonogenic growth of BPH epithelial cells. However, CM derived from Nil-treated stromal cells (Nil-CM) depicted delayed and aggressive BPH epithelial cell proliferation with increased clonogenicity of BPH epithelial cells. Further, decreased AR levels with increased cMyc transcripts and pAkt levels also validated the clonogenic transformation under the paracrine influence of inhibition of stromal-AR. Moreover, the CM of stromal-AR activation imparted positive regulation of basal/progenitor pool through LGR4, β-Catenin, and ΔNP63α expression. Hence, the present study highlighted the restricted disease progression and retains the basal/progenitor state of BPH epithelial cells through the activation of stromal-AR. On the contrary, AR-independent aggressive BPH epithelial cell growth due to paracrine action of loss stromal-AR directs us to reform AR pertaining treatment regimes for better clinical outcomes.

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Acknowledgements

We thank Dr. Ajit Gohil, Dept. of General Surgery, GMERS Hospital, Gotri, Vadodara for providing BPH patient tissue samples for the study. We also thank Dr. Vikram Sarabhai Institute of Cell and Molecular Biology for the central instrumentation facility. GC received financial support from University Grants Commission (UGC), Govt. of India, New Delhi for pursuing this work.

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  1. Avani Mehta

    Present address: Division of Biological Sciences, Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, Karnataka, 560012, India

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  1. Department of Biochemistry, The M. S. University of Baroda, Vadodara, Gujarat, 390002, India

    Gaurav Chauhan, Avani Mehta & Sarita Gupta

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GC and SG conceptualized the project. GC performed & analyzed the experiments. AM contributed to perform experiments and data analysis; GC wrote the manuscript. SG supervised the project and revised the manuscript for submission. All authors read and approved the final manuscript.

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Chauhan, G., Mehta, A. & Gupta, S. Stromal-AR influences the growth of epithelial cells in the development of benign prostate hyperplasia. Mol Cell Biochem 471, 129–142 (2020). https://doi.org/10.1007/s11010-020-03773-z

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