Bacterial Lipopolysaccharide Augmented Malignant Transformation and Promoted the Stemness in Prostate Cancer Epithelial Cells

Sijie Tang,1,2 Xueqi Lian,1 Huiying Cheng,1 Jiaqian Guo,1 Daguang Ni,1 Can Huang,1 Xiang Gu,2 Hong Meng,3 Jiajia Jiang,1 Xiaohua Li1,4,5 1The Aoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu University, Zhangjiagang, Suzhou, 215600, People’s Republic of China; 2Department of Urology, t...

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Autores principales:	Tang S, Lian X, Cheng H, Guo J, Ni D, Huang C, Gu X, Meng H, Jiang J, Li X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	tumorosphere forming prostate cancer bacterial lipopolysaccharide epithelial malignant transformation cancer stemness. Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/1097b4ba5a7146fc93d963f593ac17a1
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id	oai:doaj.org-article:1097b4ba5a7146fc93d963f593ac17a1
record_format	dspace
institution	DOAJ
collection	DOAJ
language	EN
topic	tumorosphere forming prostate cancer bacterial lipopolysaccharide epithelial malignant transformation cancer stemness. Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	tumorosphere forming prostate cancer bacterial lipopolysaccharide epithelial malignant transformation cancer stemness. Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Tang S Lian X Cheng H Guo J Ni D Huang C Gu X Meng H Jiang J Li X Bacterial Lipopolysaccharide Augmented Malignant Transformation and Promoted the Stemness in Prostate Cancer Epithelial Cells
description	Sijie Tang,1,2 Xueqi Lian,1 Huiying Cheng,1 Jiaqian Guo,1 Daguang Ni,1 Can Huang,1 Xiang Gu,2 Hong Meng,3 Jiajia Jiang,1 Xiaohua Li1,4,5 1The Aoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu University, Zhangjiagang, Suzhou, 215600, People’s Republic of China; 2Department of Urology, the Affiliated Aoyang Hospital of Jiangsu University, Zhangjiagang, Suzhou, 215600, People’s Republic of China; 3Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Detroit, MI, 48201, USA; 4The Laboratory of Clinical Genomics, Hefei KingMed Diagnostics Ltd, Hefei, 230088, People’s Republic of China; 5National Center for Gene Testing Technology Application & Demonstration (Anhui), Hefei, 230088, People’s Republic of ChinaCorrespondence: Xiaohua Li; Jiajia JiangThe Aoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu University, 279 Jingang Blvd., Zhangjiagang, Suzhou, 215600, People’s Republic of ChinaEmail joshua28li@163.com; 2111913004@stmail.ujs.edu.cnPurpose: To study bacterial lipopolysaccharide (LPS)-induced cancer stem-like transformation and to investigate the inhibitory effect of Trichostatin A (TSA) on the malignant transformation through targeting p-Stat3 signaling.Methods: 2D, 3D, and serum-free suspension culture system were used to study LPS-induced malignant transformation in series malignant grade of prostate cancer (PCa) epithelial cells. Flow cytometry assay and RT-PCR were utilized to evaluate the CD44+CD133+ stem cell population, the expression of inflammatory cytokines and series tumor stemness biomarkers. Meanwhile, Western blot was used to analyze the alteration of cell signaling associated-molecules by treatment with TSA, an original antifungal antibiotic and a panel inhibitor of histone deacetylase.Results: Our study found that LPS promoted the migration, invasion and stem-like tumoroshpere forming in multiple PCa cell lines including DU145, PC3, 22RV1, LNCaP. LPS also enriched CD44+CD133+ stem cell population and increased the expression of series tumor stemness biomarkers (e.g., CD44, CD133, SOX-2, α-intergrin, Nestin, etc.). TSA was found to prevent tumor cell migration, invasion and tumorosphere forming in DU145 and PC3 cells with increasing tumor suppressive Maspin and reducing both phosphorylation of Stat3 (p-Stat3) and pro-oncogene c-Myc expression in LPS-treated DU145 cells. Furthermore, blocking Stat3 signaling pathway by treatment with TSA and/or small molecule compound Stattic of an p-Stat3 inhibitor effectively abrogated LPS-induced tumorosphere forming with decrease of IL-6, IL-8 and stemness biomarkers CD44, SOX-2 expression.Conclusion: Our data demonstrated that the inflammatory agent of bacterial LPS augmented malignant transformation and promoted the cancerous stemness in PCa epithelial cells. TSA could prevent, at least in part, the LPS-induced malignant transformation by targeting p-Stat3/c-Myc signaling pathway and reducing inflammatory IL-6, IL-8. In addition, the assay of LPS-induced tumorosphere forming could serve as a simple and an easy handling method for targeting cancer stem cells drug screening in vitro in clinical practice.Keywords: tumorosphere forming, prostate cancer, bacterial lipopolysaccharide, epithelial malignant transformation, cancer stemness
format	article
author	Tang S Lian X Cheng H Guo J Ni D Huang C Gu X Meng H Jiang J Li X
author_facet	Tang S Lian X Cheng H Guo J Ni D Huang C Gu X Meng H Jiang J Li X
author_sort	Tang S
title	Bacterial Lipopolysaccharide Augmented Malignant Transformation and Promoted the Stemness in Prostate Cancer Epithelial Cells
title_short	Bacterial Lipopolysaccharide Augmented Malignant Transformation and Promoted the Stemness in Prostate Cancer Epithelial Cells
title_full	Bacterial Lipopolysaccharide Augmented Malignant Transformation and Promoted the Stemness in Prostate Cancer Epithelial Cells
title_fullStr	Bacterial Lipopolysaccharide Augmented Malignant Transformation and Promoted the Stemness in Prostate Cancer Epithelial Cells
title_full_unstemmed	Bacterial Lipopolysaccharide Augmented Malignant Transformation and Promoted the Stemness in Prostate Cancer Epithelial Cells
title_sort	bacterial lipopolysaccharide augmented malignant transformation and promoted the stemness in prostate cancer epithelial cells
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/1097b4ba5a7146fc93d963f593ac17a1
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spelling	oai:doaj.org-article:1097b4ba5a7146fc93d963f593ac17a12021-12-02T17:56:50ZBacterial Lipopolysaccharide Augmented Malignant Transformation and Promoted the Stemness in Prostate Cancer Epithelial Cells1178-7031https://doaj.org/article/1097b4ba5a7146fc93d963f593ac17a12021-11-01T00:00:00Zhttps://www.dovepress.com/bacterial-lipopolysaccharide-augmented-malignant-transformation-and-pr-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Sijie Tang,1,2 Xueqi Lian,1 Huiying Cheng,1 Jiaqian Guo,1 Daguang Ni,1 Can Huang,1 Xiang Gu,2 Hong Meng,3 Jiajia Jiang,1 Xiaohua Li1,4,5 1The Aoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu University, Zhangjiagang, Suzhou, 215600, People’s Republic of China; 2Department of Urology, the Affiliated Aoyang Hospital of Jiangsu University, Zhangjiagang, Suzhou, 215600, People’s Republic of China; 3Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Detroit, MI, 48201, USA; 4The Laboratory of Clinical Genomics, Hefei KingMed Diagnostics Ltd, Hefei, 230088, People’s Republic of China; 5National Center for Gene Testing Technology Application & Demonstration (Anhui), Hefei, 230088, People’s Republic of ChinaCorrespondence: Xiaohua Li; Jiajia JiangThe Aoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu University, 279 Jingang Blvd., Zhangjiagang, Suzhou, 215600, People’s Republic of ChinaEmail joshua28li@163.com; 2111913004@stmail.ujs.edu.cnPurpose: To study bacterial lipopolysaccharide (LPS)-induced cancer stem-like transformation and to investigate the inhibitory effect of Trichostatin A (TSA) on the malignant transformation through targeting p-Stat3 signaling.Methods: 2D, 3D, and serum-free suspension culture system were used to study LPS-induced malignant transformation in series malignant grade of prostate cancer (PCa) epithelial cells. Flow cytometry assay and RT-PCR were utilized to evaluate the CD44+CD133+ stem cell population, the expression of inflammatory cytokines and series tumor stemness biomarkers. Meanwhile, Western blot was used to analyze the alteration of cell signaling associated-molecules by treatment with TSA, an original antifungal antibiotic and a panel inhibitor of histone deacetylase.Results: Our study found that LPS promoted the migration, invasion and stem-like tumoroshpere forming in multiple PCa cell lines including DU145, PC3, 22RV1, LNCaP. LPS also enriched CD44+CD133+ stem cell population and increased the expression of series tumor stemness biomarkers (e.g., CD44, CD133, SOX-2, α-intergrin, Nestin, etc.). TSA was found to prevent tumor cell migration, invasion and tumorosphere forming in DU145 and PC3 cells with increasing tumor suppressive Maspin and reducing both phosphorylation of Stat3 (p-Stat3) and pro-oncogene c-Myc expression in LPS-treated DU145 cells. Furthermore, blocking Stat3 signaling pathway by treatment with TSA and/or small molecule compound Stattic of an p-Stat3 inhibitor effectively abrogated LPS-induced tumorosphere forming with decrease of IL-6, IL-8 and stemness biomarkers CD44, SOX-2 expression.Conclusion: Our data demonstrated that the inflammatory agent of bacterial LPS augmented malignant transformation and promoted the cancerous stemness in PCa epithelial cells. TSA could prevent, at least in part, the LPS-induced malignant transformation by targeting p-Stat3/c-Myc signaling pathway and reducing inflammatory IL-6, IL-8. In addition, the assay of LPS-induced tumorosphere forming could serve as a simple and an easy handling method for targeting cancer stem cells drug screening in vitro in clinical practice.Keywords: tumorosphere forming, prostate cancer, bacterial lipopolysaccharide, epithelial malignant transformation, cancer stemnessTang SLian XCheng HGuo JNi DHuang CGu XMeng HJiang JLi XDove Medical Pressarticletumorosphere formingprostate cancerbacterial lipopolysaccharideepithelial malignant transformationcancer stemness.PathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 5849-5862 (2021)

Bacterial Lipopolysaccharide Augmented Malignant Transformation and Promoted the Stemness in Prostate Cancer Epithelial Cells

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