The role of the obestatin/GPR39 system in human gastric adenocarcinomas
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Begoña O. Alén1,2, Saúl Leal-López1,2, María Otero Alén3,4, Patricia Viaño3,4, Victoria García-Castro4, Carlos S. Mosteiro1,2, Andrés Beiras3,4,5, Felipe F. Casanueva1,2,6, Rosalía Gallego2,3,5, Tomás García-Caballero3,4,5, Jesús P. Camiña1,2, Yolanda Pazos1,2
1Área de Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria de Santiago (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS), Santiago de Compostela, Spain
2CIBER Fisiopatología de la Obesidad y Nutrición, Santiago de Compostela, Spain
3IDIS, CHUS, Santiago de Compostela, Spain
4Servicio de Anatomía Patológica, CHUS, SERGAS, Santiago de Compostela, Spain
5Departamento de Ciencias Morfológicas, Universidad de Santiago de Compostela (USC), Santiago de Compostela, Spain
6Departamento de Medicina, USC, Santiago de Compostela, Spain
Yolanda Pazos, e-mail: [email protected]
Keywords: GPR39, obestatin, stomach, adenocarcinoma
Received: July 29, 2015 Accepted: November 25, 2015 Published: December 22, 2015
Obestatin, a 23-amino acid peptide encoded by the ghrelin gene, and the GPR39 receptor were reported to be involved in the control of mitogenesis of gastric cancer cell lines; however, the relationship between the obestatin/GPR39 system and gastric cancer progression remains unknown. In the present study, we determined the expression levels of the obestatin/GPR39 system in human gastric adenocarcinomas and explored their potential functional roles. Twenty-eight patients with gastric adenocarcinomas were retrospectively studied, and clinical data were obtained. The role of obestatin/GPR39 in gastric cancer progression was studied in vitro using the human gastric adenocarcinoma AGS cell line. Obestatin exogenous administration in these GPR39-bearing cells deregulated the expression of several hallmarks of the epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, obestatin signaling promoted phenotypic changes via GPR39, increasingly impacting on the cell morphology, proliferation, migration and invasion of these cells. In healthy human stomachs, obestatin expression was observed in the neuroendocrine cells and GPR39 expression was localized mainly in the chief cells of the oxyntic glands. In human gastric adenocarcinomas, no obestatin expression was found; however, an aberrant pattern of GPR39 expression was discovered, correlating to the dedifferentiation of the tumor. Altogether, our data strongly suggest the involvement of the obestatin/GPR39 system in the pathogenesis and/or clinical outcome of human gastric adenocarcinomas and highlight the potential usefulness of GPR39 as a prognostic marker in gastric cancer.
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