| Texto completo | |
| Autor(es): |
Bento, Carolina Adriane
;
Arnaud-Sampaio, Vanessa Fernandes
;
Glaser, Talita
;
Adinolfi, Elena
;
Coutinho-Silva, Robson
;
Ulrich, Henning
;
Lameu, Claudiana
Número total de Autores: 7
|
| Tipo de documento: | Artigo Científico |
| Fonte: | PURINERGIC SIGNALLING; v. N/A, p. 18-pg., 2024-10-19. |
| Resumo | |
Tumor-associated macrophages (TAMs) exhibit antitumor or protumor responses related to inflammatory (or M1) and alternative (or M2) phenotypes, respectively. The P2X7 receptor plays a key role in macrophage polarization, influencing inflammation and immunosuppression. In this study, we investigated the role of the P2X7 receptor in TAMs. Using P2X7 receptor-deficient macrophages, we analyzed gene expression profiles and their implications for neuroblastoma invasion and chemoresistance. Our results showed that P2X7 receptor deficiency altered the expression of classical polarization markers, such as nitric oxide synthase 2 (Nos2) and tumor necrosis factor-alpha (Tnf), as well as alternative phenotype markers, including mannose receptor C-type 1 (Mrc1) and arginase 1 (Arg1). P2X7 deficiency also influenced the expression of the ectonucleotidases Entpd1 and Nt5e and other purinergic receptors, especially P2ry2, suggesting compensatory mechanisms involved in macrophage polarization. In particular, TAMs deficient in P2X7 showed a phenotype with characteristics intermideiate between resting macrophages (M0) and M1 polarization rather than the M2-type phenotype like and wild-type TAM macrophages. In addition, P2rx7(-/-) TAMs regulated the expression of P2X7 receptor isoforms in neuroblastoma cells, with downregulation of the P2X7 A and B isoforms leading to a decrease in chemotherapy-induced cell death. However, TAMs expressing P2X7 downregulated only the B isoform, suggesting that TAMs play a role in modulating tumor behavior through P2X7 receptor isoform regulation. Taken together, our data underscore the regulatory function of the P2X7 receptor in orchestrating alternative macrophage polarization and in the interplay between tumor cells and TAMs. These findings help to clarify the complex interplay of purinergic signaling in cancer progression and open up avenues for future research and therapeutic interventions. (AU) | |
| Processo FAPESP: | 18/14993-5 - Influência dos fenótipos M1 e M2 de macrófagos e do receptor P2X7 na metástase de neuroblastoma |
| Beneficiário: | Carolina Adriane Bento |
| Modalidade de apoio: | Bolsas no Brasil - Mestrado |
| Processo FAPESP: | 22/11093-9 - Sinalização purinérgica na transição fenotípica de macrófagos associados a tumor (TAMs) e Células Tumorais Circulantes (CTCs) para metástase cerebral de Câncer de Mama |
| Beneficiário: | Claudiana Lameu |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 18/07366-4 - Receptores de purinas e cininas como alvos de estudo e intervenção terapêutica em doenças neurológicas |
| Beneficiário: | Alexander Henning Ulrich |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 15/19128-2 - Mecanismos de metástase de tumores infantis para a medula óssea |
| Beneficiário: | Claudiana Lameu |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |