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HER2 as a potential therapeutic target on quiescent prostate cancer cells

Quiescent prostate cancer (PCa) cells are common in tumors but are often resistant to chemotherapy. Quiescent PCa cells are also enriched for a stem-like tumor initiating population, and can lead to recurrence after dormancy. Unfortunately, quiescent PCa cells are difficult to identify and / or targ...

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Autores principales: Yumoto, Kenji, Rashid, Jibraan, Ibrahim, Kristina G., Zielske, Steven P., Wang, Yu, Omi, Maiko, Decker, Ann M., Jung, Younghun, Sun, Dan, Remmer, Henriette A., Mishina, Yuji, Buttitta, Laura A., Taichman, Russell S., Cackowski, Frank C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9971552/
https://www.ncbi.nlm.nih.gov/pubmed/36805918
http://dx.doi.org/10.1016/j.tranon.2023.101642
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author Yumoto, Kenji
Rashid, Jibraan
Ibrahim, Kristina G.
Zielske, Steven P.
Wang, Yu
Omi, Maiko
Decker, Ann M.
Jung, Younghun
Sun, Dan
Remmer, Henriette A.
Mishina, Yuji
Buttitta, Laura A.
Taichman, Russell S.
Cackowski, Frank C.
author_facet Yumoto, Kenji
Rashid, Jibraan
Ibrahim, Kristina G.
Zielske, Steven P.
Wang, Yu
Omi, Maiko
Decker, Ann M.
Jung, Younghun
Sun, Dan
Remmer, Henriette A.
Mishina, Yuji
Buttitta, Laura A.
Taichman, Russell S.
Cackowski, Frank C.
author_sort Yumoto, Kenji
collection PubMed
description Quiescent prostate cancer (PCa) cells are common in tumors but are often resistant to chemotherapy. Quiescent PCa cells are also enriched for a stem-like tumor initiating population, and can lead to recurrence after dormancy. Unfortunately, quiescent PCa cells are difficult to identify and / or target with treatment in part because the relevant markers are intracellular and regulated by protein stability. We addressed this problem by utilizing PCa cells expressing fluorescent markers for CDKN1B (p27) and CDT1, which can separate viable PCa cells into G(0), G(1), or combined S/G(2)/M populations. We used FACS to collect G(1) and G(0) PC3 PCa cells, isolated membrane proteins, and analyzed protein abundance in G(0) vs G(1) cells by gas chromatography mass spectrometry. Enrichment analysis identified nucleocytoplasmic transport as the most significantly different pathway. To identify cell surface proteins potentially identifying quiescent PCa cells for future patient samples or for antibody based therapeutic research, we focused on differentially abundant plasma membrane proteins, and identified ERBB2 (HER2) as a cell surface protein enriched on G(0) PCa cells. High HER2 on the cell membrane is associated with quiescence in PCa cells and likely induced by the bone microenvironment. Using a drug conjugated anti-HER2 antibody (trastuzumab emtansine) in a mouse PCa xenograft model delayed metastatic tumor growth, suggesting approaches that target HER2-high cells may be beneficial in treating PCa. We propose that HER2 is deserving of further study in PCa as a target on quiescent cells to prevent recurrence, decrease chemotherapy resistance, or eradicate minimal residual disease.
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spelling pubmed-99715522023-03-01 HER2 as a potential therapeutic target on quiescent prostate cancer cells Yumoto, Kenji Rashid, Jibraan Ibrahim, Kristina G. Zielske, Steven P. Wang, Yu Omi, Maiko Decker, Ann M. Jung, Younghun Sun, Dan Remmer, Henriette A. Mishina, Yuji Buttitta, Laura A. Taichman, Russell S. Cackowski, Frank C. Transl Oncol Original Research Quiescent prostate cancer (PCa) cells are common in tumors but are often resistant to chemotherapy. Quiescent PCa cells are also enriched for a stem-like tumor initiating population, and can lead to recurrence after dormancy. Unfortunately, quiescent PCa cells are difficult to identify and / or target with treatment in part because the relevant markers are intracellular and regulated by protein stability. We addressed this problem by utilizing PCa cells expressing fluorescent markers for CDKN1B (p27) and CDT1, which can separate viable PCa cells into G(0), G(1), or combined S/G(2)/M populations. We used FACS to collect G(1) and G(0) PC3 PCa cells, isolated membrane proteins, and analyzed protein abundance in G(0) vs G(1) cells by gas chromatography mass spectrometry. Enrichment analysis identified nucleocytoplasmic transport as the most significantly different pathway. To identify cell surface proteins potentially identifying quiescent PCa cells for future patient samples or for antibody based therapeutic research, we focused on differentially abundant plasma membrane proteins, and identified ERBB2 (HER2) as a cell surface protein enriched on G(0) PCa cells. High HER2 on the cell membrane is associated with quiescence in PCa cells and likely induced by the bone microenvironment. Using a drug conjugated anti-HER2 antibody (trastuzumab emtansine) in a mouse PCa xenograft model delayed metastatic tumor growth, suggesting approaches that target HER2-high cells may be beneficial in treating PCa. We propose that HER2 is deserving of further study in PCa as a target on quiescent cells to prevent recurrence, decrease chemotherapy resistance, or eradicate minimal residual disease. Neoplasia Press 2023-02-18 /pmc/articles/PMC9971552/ /pubmed/36805918 http://dx.doi.org/10.1016/j.tranon.2023.101642 Text en © 2023 The Authors. Published by Elsevier Inc. https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Original Research
Yumoto, Kenji
Rashid, Jibraan
Ibrahim, Kristina G.
Zielske, Steven P.
Wang, Yu
Omi, Maiko
Decker, Ann M.
Jung, Younghun
Sun, Dan
Remmer, Henriette A.
Mishina, Yuji
Buttitta, Laura A.
Taichman, Russell S.
Cackowski, Frank C.
HER2 as a potential therapeutic target on quiescent prostate cancer cells
title HER2 as a potential therapeutic target on quiescent prostate cancer cells
title_full HER2 as a potential therapeutic target on quiescent prostate cancer cells
title_fullStr HER2 as a potential therapeutic target on quiescent prostate cancer cells
title_full_unstemmed HER2 as a potential therapeutic target on quiescent prostate cancer cells
title_short HER2 as a potential therapeutic target on quiescent prostate cancer cells
title_sort her2 as a potential therapeutic target on quiescent prostate cancer cells
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9971552/
https://www.ncbi.nlm.nih.gov/pubmed/36805918
http://dx.doi.org/10.1016/j.tranon.2023.101642
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