P2Y₂ receptor activation promotes esophageal cancer cells proliferation via ERK1/2 pathway

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Zaparte, Aline ; Cappellari, Angelica R. ; Brandao, Caroline A. ; de Souza, Julia B. ; Borges, Thiago J. ; Kist, Luiza W. ; Bogo, Mauricio R. ; Zerbini, Luiz F. ; Ribeiro Pinto, Luis Felipe ; Glaser, Talita ; Goncalves, Maria Carolina B. ; Naaldijk, Yahaira ; Ulrich, Henning ; Morrone, Fernanda B.

• Document type: Journal article
• Source: European Journal of Pharmacology; v. 891, p. 12-pg., 2021-01-15.

Abstract

Esophageal cancer is a prominent worldwide illness that is divided into two main subtypes: esophageal squamous cell carcinoma and esophageal adenocarcinoma. Mortality rates are alarming, and the understanding of the mechanisms involved in esophageal cancer development, becomes essential. Purinergic signaling is related to many diseases and among these various types of tumors. Here we studied the effects of the P2Y(2) receptor activation in different types of esophageal cancer. Esophageal tissue samples of healthy controls were used for P2Y(2)R expression quantification. Two human esophageal cancer cell lines Kyse-450 (squamous cell carcinoma) and OE-33 (adenocarcinoma) were used to perform in vitro analysis of cell proliferation, migration, adhesion, and the signaling pathways involved in P2Y(2)R activation. Data showed that P2Y(2)R was expressed in biopsies of patients with ESCC and adenocarcinoma, as well as in the two human esophageal cancer cell lines studied. The RT-qPCR analysis demonstrated that OE-33 cells have higher P2RY2 expression than Kyse-450 squamous cell line. Results showed that P2Y(2)R activation, induced by ATP or UTP, promoted esophageal cancer cells proliferation and colony formation. P2Y(2)R blockage with the selective antagonist, AR-C 118925XX, led to decreased proliferation, colony formation and adhesion. Treatments with ATP or UTP activated ERK 1/2 pathway in ESCC and ECA cells. The P2Y(2)R antagonism did not alter the migration of esophageal cancer cells. Interestingly, the esophageal cancer cell lines presented a distinct profile of nucleotide hydrolysis activity. The modulation of P2Y(2) receptors may be a promising target for esophageal cancer treatment. (AU)

• FAPESP's process: 12/50880-4 - Stem cells: from basic studies of kinin and purinergic receptor roles towards therapeutical applications
• Grantee: Alexander Henning Ulrich
• Support Opportunities: Research Projects - Thematic Grants