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Effect of Tumor Burden on Tumor Aggressiveness and Immune Modulation in Prostate Cancer: Association with IL-6 Signaling

Local treatment is known to improve survival in men with locally advanced prostate cancer (LAPC), but the underlying mechanisms remain unclear. In the present study, we examined the role of tumor burden in tumor aggressiveness, as well as the pathway responsible for these changes. We used human and...

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Autores principales: Wu, Chun-Te, Huang, Yun-Ching, Chen, Wen-Cheng, Chen, Miao-Fen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678422/
https://www.ncbi.nlm.nih.gov/pubmed/31315262
http://dx.doi.org/10.3390/cancers11070992
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author Wu, Chun-Te
Huang, Yun-Ching
Chen, Wen-Cheng
Chen, Miao-Fen
author_facet Wu, Chun-Te
Huang, Yun-Ching
Chen, Wen-Cheng
Chen, Miao-Fen
author_sort Wu, Chun-Te
collection PubMed
description Local treatment is known to improve survival in men with locally advanced prostate cancer (LAPC), but the underlying mechanisms remain unclear. In the present study, we examined the role of tumor burden in tumor aggressiveness, as well as the pathway responsible for these changes. We used human and murine prostate cancer cell lines to examine the role of tumor burden in tumor aggressiveness, as well as its correlation with cancer stem cell (CSC) marker levels and IL-6 signaling. Furthermore, 167 prostate cancer biopsy specimens were analyzed in terms of correlations of IL-6 and CD44 levels with clinical patient characteristics. Data from preclinical models showed that larger tumor burden was associated with more aggressive tumor growth associated and increased CD44 expression. Using cellular experiments and orthotopic tumor models, we showed that CD44+ prostate cancer cells have CSC-like properties, enhanced epithelial–mesenchymal transition (EMT), and a more immunosuppressive microenvironment. There was a significant correlation between IL-6 and CD44 levels based on in vitro testing of clinical samples. Blockade of IL-6/STAT3 signaling attenuated the expression of CD44, CSC-like properties, and aggressive tumor behavior in vitro and in vivo. In conclusion, CD44 expression is significantly associated with tumor aggressiveness in prostate cancer and activation of IL-6 signaling leads to a suitable microenvironment for the induction of CD44 expression. Based on our study, reduced tumor burden was associated with attenuated IL-6 signaling and augmented tumor rejection in the microenvironment, which might mediate the benefit of clinical adoption with aggressive local therapy.
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spelling pubmed-66784222019-08-19 Effect of Tumor Burden on Tumor Aggressiveness and Immune Modulation in Prostate Cancer: Association with IL-6 Signaling Wu, Chun-Te Huang, Yun-Ching Chen, Wen-Cheng Chen, Miao-Fen Cancers (Basel) Article Local treatment is known to improve survival in men with locally advanced prostate cancer (LAPC), but the underlying mechanisms remain unclear. In the present study, we examined the role of tumor burden in tumor aggressiveness, as well as the pathway responsible for these changes. We used human and murine prostate cancer cell lines to examine the role of tumor burden in tumor aggressiveness, as well as its correlation with cancer stem cell (CSC) marker levels and IL-6 signaling. Furthermore, 167 prostate cancer biopsy specimens were analyzed in terms of correlations of IL-6 and CD44 levels with clinical patient characteristics. Data from preclinical models showed that larger tumor burden was associated with more aggressive tumor growth associated and increased CD44 expression. Using cellular experiments and orthotopic tumor models, we showed that CD44+ prostate cancer cells have CSC-like properties, enhanced epithelial–mesenchymal transition (EMT), and a more immunosuppressive microenvironment. There was a significant correlation between IL-6 and CD44 levels based on in vitro testing of clinical samples. Blockade of IL-6/STAT3 signaling attenuated the expression of CD44, CSC-like properties, and aggressive tumor behavior in vitro and in vivo. In conclusion, CD44 expression is significantly associated with tumor aggressiveness in prostate cancer and activation of IL-6 signaling leads to a suitable microenvironment for the induction of CD44 expression. Based on our study, reduced tumor burden was associated with attenuated IL-6 signaling and augmented tumor rejection in the microenvironment, which might mediate the benefit of clinical adoption with aggressive local therapy. MDPI 2019-07-16 /pmc/articles/PMC6678422/ /pubmed/31315262 http://dx.doi.org/10.3390/cancers11070992 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wu, Chun-Te
Huang, Yun-Ching
Chen, Wen-Cheng
Chen, Miao-Fen
Effect of Tumor Burden on Tumor Aggressiveness and Immune Modulation in Prostate Cancer: Association with IL-6 Signaling
title Effect of Tumor Burden on Tumor Aggressiveness and Immune Modulation in Prostate Cancer: Association with IL-6 Signaling
title_full Effect of Tumor Burden on Tumor Aggressiveness and Immune Modulation in Prostate Cancer: Association with IL-6 Signaling
title_fullStr Effect of Tumor Burden on Tumor Aggressiveness and Immune Modulation in Prostate Cancer: Association with IL-6 Signaling
title_full_unstemmed Effect of Tumor Burden on Tumor Aggressiveness and Immune Modulation in Prostate Cancer: Association with IL-6 Signaling
title_short Effect of Tumor Burden on Tumor Aggressiveness and Immune Modulation in Prostate Cancer: Association with IL-6 Signaling
title_sort effect of tumor burden on tumor aggressiveness and immune modulation in prostate cancer: association with il-6 signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678422/
https://www.ncbi.nlm.nih.gov/pubmed/31315262
http://dx.doi.org/10.3390/cancers11070992
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