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| Autor(es): Mostrar menos - |
Baldavira, Camila Machado
;
Qualiotto, Aline Nery
;
Prieto, Tabatha Gutierrez
;
de Morais Fernezlian, Sandra
;
Assato, Aline
;
Balancin, Marcelo
;
Takagaki, Teresa
;
Ab'Saber, Alexandre
;
Velosa, Ana Paula Pereira
;
Teodoro, Walcy Rosolia
;
Capelozzi, Vera Luiza
Número total de Autores: 11
|
| Tipo de documento: | Artigo Científico |
| Fonte: | GLYCOCONJUGATE JOURNAL; v. N/A, p. 12-pg., 2025-08-13. |
| Resumo | |
The study aimed to verify whether the expression of glycosaminoglycans (GAGs) and proteoglycans (PGs) in the tumor matrix affects the plasticity of mesothelioma and its relationship with the phenotype, progression, and resistance to treatment of malignant mesothelioma (MM). As MM is highly aggressive, understanding the molecular mechanisms that regulate the abilities of tumor cells to alter their behaviors and shapes is essential to the development of new therapeutic strategies. To test this hypothesis, we studied 66 samples of human biphasic MM. The expression levels of the GAGs heparan sulfate (HS) and chondroitin sulfate (SC), as well as the PGs versican, biglycan, and perlecan were detected using immunohistochemistry, and their expression was quantified using semi-automated digital analysis. We found that the fusiform phenotype of MM cells was associated with higher expression levels of HS, versican, and biglycan (all P-values < 0.001) in the extracellular matrix. This suggests that the increase and eventual rapid turnover of cell membrane PGs resulted in a variation in shape from polygonal to fusiform phenotypes, whereas GAGs were associated with cell aggregation-thus indicating the distinct functions of different GAGs. Multivariate Cox regression analysis showed that non-surgical patients (hazard ratio [HR]: 4.03 (1.26-12.82); P = 0.02), whose tumors presented necrosis (P < 0.001), high HS expression (P = 0.02), and low biglycan expression (HR: 2.68 [1.16-6.18]; P = 0.02) had significantly worse overall survival rates. We concluded that the expression of GAGs and PGs in the ECM affects the plasticity of MM, modifies its phenotype, and facilitates both its progression and resistance to treatment. (AU) | |
| Processo FAPESP: | 23/09682-9 - Modelagem da matriz extracelular e da transição epitelial-mesenquimal por gradiente histomolecular em neoplasia neuroendócrina pulmonar para decisões clínicas |
| Beneficiário: | Tabatha Gutierrez Prieto Martins Rocha |
| Modalidade de apoio: | Bolsas no Brasil - Programa Fixação de Jovens Doutores |
| Processo FAPESP: | 23/08136-0 - Estudo quantitativo de glicosaminoglicanos e proteoglicanos na matriz extracelular de espécimes cirúrgicos de mesotelioma pleural maligno. |
| Beneficiário: | Aline Nery Qualiotto |
| Modalidade de apoio: | Bolsas no Brasil - Iniciação Científica |
| Processo FAPESP: | 23/01158-9 - Modelagem da matriz extracelular e da transição epitelial-mesenquimal por gradiente histomolecular em neoplasia neuroendócrina pulmonar para decisões clínicas |
| Beneficiário: | Vera Luiza Capelozzi |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 18/20403-6 - Marcadores biomoleculares de proliferação e remodelamento em doenças respiratórias agudas e crônicas: promissores alvos terapêuticos |
| Beneficiário: | Vera Luiza Capelozzi |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 23/02755-0 - Avaliação da expressão proteica da transição epitélio-mesenquimal como nova perspectiva em biomarcadores para a determinação do prognóstico, resposta e resistência à terapia alvo nos carcinomas pulmonares não pequenas células |
| Beneficiário: | Camila Machado Baldavira |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |