title: Potential role of P2X7R in esophageal squamous cell carcinoma proliferation.
abstract: Esophageal cancer is an aggressive tumor and is the sixth leading cause of cancer death worldwide. ATP is well known to regulate cancer progression in a variety of models by different mechanisms, including P2X7R activation. This study aimed to evaluate the role of P2X7R in esophageal squamous cell carcinoma (ESCC) proliferation. Our results show that treatment with high ATP concentrations induced a decrease in cell number, cell viability, number of polyclonal colonies, and reduced migration of ESCC. The treatment with the selective P2X7R antagonist A740003 or siRNA for P2X7 reverted this effect in the KYSE450 cell line. In addition, results showed that P2X7R is highly expressed, at mRNA and protein levels, in KYSE450 lineage. Additionally, KYSE450, KYSE30, and OE21 cells express P2X3R, P2X4R, P2X5R, P2X6R, and P2X7R genes. P2X1R is expressed by KYSE30 and KYSE450, and only KYSE450 expresses the P2X2R gene. Furthermore, esophageal cancer cell line KYSE450 presented higher expression of E-NTPDases 1 and 2 and of Ecto-5'-NT/CD73 when compared to normal cells. This cell line also exhibits ATPase, ADPase, and AMPase activity, although in different levels, and the co-treatment of apyrase was able to revert the antiproliferative effects of ATP. Moreover, results showed high immunostaining for P2X7R in biopsies of patients with esophageal carcinoma, indicating the involvement of this receptor in the growth of this type of cancer. The results suggest that P2X7R may be a potential pharmacological target to treat ESCC and can lead us to further investigate the effect of this receptor in cancer cell progression.
authors.affiliation: Programa de Pós-Graduação em Biologia Celular e Molecular, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: André A
authors.initials: AA
authors.lastname: Santos
authors.affiliation: Programa de Pós-Graduação em Biologia Celular e Molecular, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Angélica R
authors.initials: AR
authors.lastname: Cappellari
authors.affiliation: Faculdade de Farmácia, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Fernanda O
authors.initials: FO
authors.lastname: de Marchi
authors.affiliation: Programa de Pós-Graduação em Biologia Celular e Molecular, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Marina P
authors.initials: MP
authors.lastname: Gehring
authors.affiliation: Programa de Pós-graduação em Medicina e Ciências da Saúde, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Zaparte
authors.affiliation: Faculdade de Medicina, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Brandão
authors.affiliation: Hospital São Lucas da PUCRS, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Tiago Giuliani
authors.initials: TG
authors.lastname: Lopes
authors.affiliation: Programa de Pós-graduação em Medicina e Ciências da Saúde, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.|Faculdade de Medicina, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.|Hospital São Lucas da PUCRS, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Vinicius D
authors.initials: VD
authors.lastname: da Silva
authors.affiliation: Programa de Carcinogênese Molecular, Coordenação de Pesquisa, Instituto Nacional do Câncer (INCA), Rio de Janeiro, Brazil.|Departamento de Bioquímica, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Luis Felipe Ribeiro
authors.initials: LFR
authors.lastname: Pinto
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Luiz Eduardo Baggio
authors.initials: LEB
authors.lastname: Savio
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Aline Cristina Abreu
authors.initials: ACA
authors.lastname: Moreira-Souza
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Robson
authors.initials: R
authors.lastname: Coutinho-Silva
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB), Cancer Genomics Group, Cape Town, South Africa.
authors.forename: Juliano D
authors.initials: JD
authors.lastname: Paccez
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB), Cancer Genomics Group, Cape Town, South Africa.|Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Luiz F
authors.initials: LF
authors.lastname: Zerbini
authors.affiliation: Programa de Pós-Graduação em Biologia Celular e Molecular, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil. fernanda.morrone@pucrs.br.|Faculdade de Farmácia, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil. fernanda.morrone@pucrs.br.|Programa de Pós-graduação em Medicina e Ciências da Saúde, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil. fernanda.morrone@pucrs.br.
authors.forename: Fernanda B
authors.initials: FB
authors.lastname: Morrone
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism; D000077277:Esophageal Squamous Cell Carcinoma; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics*; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*
chemical_list: C546468:P2RX7 protein, human; D034741:RNA, Small Interfering; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate
keywords: ATP; Ectonucleotidases; Esophageal cancer; P2X7R; Proliferation