Investigação da ação dos receptores purinérgicos P2Y2 e P2Y12 na proliferação de células de carcinoma escamoso e adenocarcinoma de esôfago

• Ano de defesa: 2018
• Autor(a) principal: Zaparte, Aline
• Orientador(a): Morrone, Fernanda Bueno
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Pontifícia Universidade Católica do Rio Grande do Sul
• Programa de Pós-Graduação: Programa de Pós-Graduação em Medicina e Ciências da Saúde
• Departamento: Escola de Medicina
• País: Brasil
• Palavras-chave em Português: Adenocarcinoma; Carcinoma de Células Escamosas; Esôfago; Receptores Purinérgicos P2Y; Nucleotídeos
• Área do conhecimento CNPq: CIENCIAS DA SAUDE::MEDICINA
• Link de acesso: http://tede2.pucrs.br/tede2/handle/tede/8275

Esophageal cancer, in general, is diagnosed at an advanced stage, which leads to impairment in the therapies employed, resulting in a high mortality rate. It is classified into two subtypes: adenocarcinoma and squamous cell carcinoma; both differ in histology, etiology and epidemiology. Purinergic signaling uses nucleotides and nucleosides in the extracellular medium as signaling molecules, and has been linked to different types of carcinomas. These molecules bind to G-protein coupled adenosine receptors, characterized as P1 (A1, A2A, A2B and A3), to P2X ionotropic receptors (P2X1-P2X7), and to P2Y receptors (P2Y 1, 2, 4, 6, 11, 12, 13 14), coupled to G protein. Given the evidence described in the literature and the lack of data correlating purinergic signaling with esophageal cancer, we analyzed the role of P2Y2 (P2Y2R) and P2Y12 (P2Y12R) receptors in the processes of proliferation, colony formation capacity, migration, adhesion, enzymatic activity of the ectonucleotidases and signaling pathways after the nucleotide stimulation. For this, we used the Kyse- 30 and Kyse-450 cells, representative of squamous cell carcinoma, and the OE-33 line, representative of adenocarcinoma. Also, we verified the expression of P2Y2R in biopsies of patients with squamous cell carcinoma and adenocarcinoma, compared to non-neoplastic tissues. We observed that the biopsy specimens express the P2Y2 receptor, but at different labeling intensities. The cell lines expressing P2Y2 and P2Y12R, have different responses to the stimulus with the nucleotides ADP, ATP and UTP, but the blockade of these receptors leads to a decrease in proliferation, polyclonal population formation, adhesion and migration. Regarding the pathways related to the action of P2Y2R, we verified the activation of ERK1 / 2 and Akt at different times after the stimulation with ATP and UTP. The data presented in this study demonstrate that the modulation of purinergic receptors P2Y2 and P2Y12 may become a promising tool for achieving efficacy in the treatment of esophageal cancer.