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GLRX3, a novel cancer stem cell-related secretory biomarker of pancreatic ductal adenocarcinoma.
Jo, Jung Hyun; Kim, Sun A; Lee, Jeong Hoon; Park, Yu Rang; Kim, Chanyang; Park, Soo Been; Jung, Dawoon E; Lee, Hee Seung; Chung, Moon Jae; Song, Si Young.
Afiliación
  • Jo JH; Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.
  • Kim SA; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, 03722, South Korea.
  • Lee JH; Cowell Biodigm Co., Ltd, Seoul, South Korea.
  • Park YR; Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, 03722, South Korea.
  • Kim C; Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, 03722, South Korea.
  • Park SB; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, 03722, South Korea.
  • Jung DE; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, 03722, South Korea.
  • Lee HS; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, 03722, South Korea.
  • Chung MJ; Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.
  • Song SY; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, 03722, South Korea.
BMC Cancer ; 21(1): 1241, 2021 Nov 18.
Article en En | MEDLINE | ID: mdl-34794402
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Células Madre Neoplásicas / Proteínas Portadoras / Carcinoma Ductal Pancreático / Proteínas de Neoplasias Tipo de estudio: Diagnostic_studies Límite: Animals / Humans / Male Idioma: En Revista: BMC Cancer Asunto de la revista: NEOPLASIAS Año: 2021 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Células Madre Neoplásicas / Proteínas Portadoras / Carcinoma Ductal Pancreático / Proteínas de Neoplasias Tipo de estudio: Diagnostic_studies Límite: Animals / Humans / Male Idioma: En Revista: BMC Cancer Asunto de la revista: NEOPLASIAS Año: 2021 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Reino Unido