Felix Oelrich1, Heike Junker1, Matthias B Stope2, Holger H H Erb3, Reinhard Walther1, Simone Venz1, Uwe Zimmermann4. 1. Department of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Greifswald, Germany. 2. Department of Gynecology and Gynecological Oncology, University Hospital Bonn, Bonn, Germany matthias.stope@ukbonn.de. 3. Department of Urology, Technische Universität Dresden, Dresden, Germany. 4. Department of Urology, University Medicine Greifswald, Greifswald, Germany.
Abstract
BACKGROUND/AIM: Interleukin 6 (IL6) is increased in patients with progressive prostate cancer and induces its transdifferentiation to neuroendocrine prostate cancer. Neuroendocrine prostate cancer has become one of the greatest challenges in treating castration-resistant disease and is linked to poor prognosis. It is necessary to understand better the cellular events associated with IL6-mediated neuroendocrine differentiation to prevent it and identify potential new therapeutic targets. MATERIALS AND METHODS: In the present study, an IL6-inducible neuroendocrine differentiation model established specifically for this purpose was applied using LNCaP cells. Proteomics and western blot analyses were used to identify proteins involved in neuroendocrine differentiation. Subsequently, the role of gelsolin (GSN) in the neuroendocrine differentiation model was characterized (knock-down analyses, microscopic co-localization analyses, apoptosis assay) and GSN expression levels in patient material were investigated. RESULTS: This study revealed that GSN is a crucial factor in the neuroendocrine differentiation process. CONCLUSION: It was shown that siRNA-mediated knock-down of GSN can inhibit neuroendocrine differentiation, making it a valid target for preventing IL6-mediated neuroendocrine differentiation.
BACKGROUND/AIM: Interleukin 6 (IL6) is increased in patients with progressive prostate cancer and induces its transdifferentiation to neuroendocrine prostate cancer. Neuroendocrine prostate cancer has become one of the greatest challenges in treating castration-resistant disease and is linked to poor prognosis. It is necessary to understand better the cellular events associated with IL6-mediated neuroendocrine differentiation to prevent it and identify potential new therapeutic targets. MATERIALS AND METHODS: In the present study, an IL6-inducible neuroendocrine differentiation model established specifically for this purpose was applied using LNCaP cells. Proteomics and western blot analyses were used to identify proteins involved in neuroendocrine differentiation. Subsequently, the role of gelsolin (GSN) in the neuroendocrine differentiation model was characterized (knock-down analyses, microscopic co-localization analyses, apoptosis assay) and GSN expression levels in patient material were investigated. RESULTS: This study revealed that GSN is a crucial factor in the neuroendocrine differentiation process. CONCLUSION: It was shown that siRNA-mediated knock-down of GSN can inhibit neuroendocrine differentiation, making it a valid target for preventing IL6-mediated neuroendocrine differentiation.
Authors: Alicia-Marie K Beier; Martin Puhr; Matthias B Stope; Christian Thomas; Holger H H Erb Journal: J Cancer Res Clin Oncol Date: 2022-09-23 Impact factor: 4.322
Authors: Celina Ebersbach; Alicia-Marie K Beier; Pia Hönscheid; Christian Sperling; Korinna Jöhrens; Gustavo B Baretton; Christian Thomas; Ulrich Sommer; Angelika Borkowetz; Holger H H Erb Journal: Life (Basel) Date: 2022-02-06