GLRX3, a novel cancer stem cell-related secretory biomarker of pancreatic ductal adenocarcinoma

Abstract Background Cancer stem cells (CSCs) are implicated in carcinogenesis, cancer progression, and recurrence. Several biomarkers have been described for pancreatic ductal adenocarcinoma (PDAC) CSCs; however, their function and mechanism remain unclear. Method In this study, secretome analysis w...

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Autores principales:	Jung Hyun Jo, Sun A Kim, Jeong Hoon Lee, Yu Rang Park, Chanyang Kim, Soo Been Park, Dawoon E. Jung, Hee Seung Lee, Moon Jae Chung, Si Young Song
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Pancreatic cancer Cancer stem cell Biomarker Glutaredoxin 3 GLRX3 Stemness Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/eb3af251a62c4c54b9cc1856215d522c
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spelling	oai:doaj.org-article:eb3af251a62c4c54b9cc1856215d522c2021-11-21T12:30:18ZGLRX3, a novel cancer stem cell-related secretory biomarker of pancreatic ductal adenocarcinoma10.1186/s12885-021-08898-y1471-2407https://doaj.org/article/eb3af251a62c4c54b9cc1856215d522c2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12885-021-08898-yhttps://doaj.org/toc/1471-2407Abstract Background Cancer stem cells (CSCs) are implicated in carcinogenesis, cancer progression, and recurrence. Several biomarkers have been described for pancreatic ductal adenocarcinoma (PDAC) CSCs; however, their function and mechanism remain unclear. Method In this study, secretome analysis was performed in pancreatic CSC-enriched spheres and control adherent cells for biomarker discovery. Glutaredoxin3 (GLRX3), a novel candidate upregulated in spheres, was evaluated for its function and clinical implication. Results PDAC CSC populations, cell lines, patient tissues, and blood samples demonstrated GLRX3 overexpression. In contrast, GLRX3 silencing decreased the in vitro proliferation, migration, clonogenicity, and sphere formation of cells. GLRX3 knockdown also reduced tumor formation and growth in vivo. GLRX3 was found to regulate Met/PI3K/AKT signaling and stemness-related molecules. ELISA results indicated GLRX3 overexpression in the serum of patients with PDAC compared to that in healthy controls. The sensitivity and specificity of GLRX3 for PDAC diagnosis were 80.0 and 100%, respectively. When GLRX3 and CA19–9 were combined, sensitivity was significantly increased to 98.3% compared to that with GLRX3 or CA19–9 alone. High GLRX3 expression was also associated with poor disease-free survival in patients receiving curative surgery. Conclusion Overall, these results indicate GLRX3 as a novel diagnostic marker and therapeutic target for PDAC targeting CSCs.Jung Hyun JoSun A KimJeong Hoon LeeYu Rang ParkChanyang KimSoo Been ParkDawoon E. JungHee Seung LeeMoon Jae ChungSi Young SongBMCarticlePancreatic cancerCancer stem cellBiomarkerGlutaredoxin 3GLRX3StemnessNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBMC Cancer, Vol 21, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pancreatic cancer Cancer stem cell Biomarker Glutaredoxin 3 GLRX3 Stemness Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Pancreatic cancer Cancer stem cell Biomarker Glutaredoxin 3 GLRX3 Stemness Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jung Hyun Jo Sun A Kim Jeong Hoon Lee Yu Rang Park Chanyang Kim Soo Been Park Dawoon E. Jung Hee Seung Lee Moon Jae Chung Si Young Song GLRX3, a novel cancer stem cell-related secretory biomarker of pancreatic ductal adenocarcinoma
description	Abstract Background Cancer stem cells (CSCs) are implicated in carcinogenesis, cancer progression, and recurrence. Several biomarkers have been described for pancreatic ductal adenocarcinoma (PDAC) CSCs; however, their function and mechanism remain unclear. Method In this study, secretome analysis was performed in pancreatic CSC-enriched spheres and control adherent cells for biomarker discovery. Glutaredoxin3 (GLRX3), a novel candidate upregulated in spheres, was evaluated for its function and clinical implication. Results PDAC CSC populations, cell lines, patient tissues, and blood samples demonstrated GLRX3 overexpression. In contrast, GLRX3 silencing decreased the in vitro proliferation, migration, clonogenicity, and sphere formation of cells. GLRX3 knockdown also reduced tumor formation and growth in vivo. GLRX3 was found to regulate Met/PI3K/AKT signaling and stemness-related molecules. ELISA results indicated GLRX3 overexpression in the serum of patients with PDAC compared to that in healthy controls. The sensitivity and specificity of GLRX3 for PDAC diagnosis were 80.0 and 100%, respectively. When GLRX3 and CA19–9 were combined, sensitivity was significantly increased to 98.3% compared to that with GLRX3 or CA19–9 alone. High GLRX3 expression was also associated with poor disease-free survival in patients receiving curative surgery. Conclusion Overall, these results indicate GLRX3 as a novel diagnostic marker and therapeutic target for PDAC targeting CSCs.
format	article
author	Jung Hyun Jo Sun A Kim Jeong Hoon Lee Yu Rang Park Chanyang Kim Soo Been Park Dawoon E. Jung Hee Seung Lee Moon Jae Chung Si Young Song
author_facet	Jung Hyun Jo Sun A Kim Jeong Hoon Lee Yu Rang Park Chanyang Kim Soo Been Park Dawoon E. Jung Hee Seung Lee Moon Jae Chung Si Young Song
author_sort	Jung Hyun Jo
title	GLRX3, a novel cancer stem cell-related secretory biomarker of pancreatic ductal adenocarcinoma
title_short	GLRX3, a novel cancer stem cell-related secretory biomarker of pancreatic ductal adenocarcinoma
title_full	GLRX3, a novel cancer stem cell-related secretory biomarker of pancreatic ductal adenocarcinoma
title_fullStr	GLRX3, a novel cancer stem cell-related secretory biomarker of pancreatic ductal adenocarcinoma
title_full_unstemmed	GLRX3, a novel cancer stem cell-related secretory biomarker of pancreatic ductal adenocarcinoma
title_sort	glrx3, a novel cancer stem cell-related secretory biomarker of pancreatic ductal adenocarcinoma
publisher	BMC
publishDate	2021
url	https://doaj.org/article/eb3af251a62c4c54b9cc1856215d522c
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GLRX3, a novel cancer stem cell-related secretory biomarker of pancreatic ductal adenocarcinoma

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