Publicação
Studying the impact of aberrant glycosylated extracellular vesicles on gastric cancer recipient cells
| Resumo: | Glycans are important molecules involved in various cellular functions, particularly in cell-cell interactions at the cell membrane. In cancer, abnormal glycosylation disrupts cellular processes and contributes to increased malignancy. Specifically, truncated O-glycans like sialyl-Tn (STn) have been linked to invasiveness and poor prognosis in cancer patients. This study investigated how truncated O-glycans modulate gastric cancer cells through extracellular vesicles (EVs) carrying the same glycosignature. EVs are small structures released by cells that transport cargo and trigger signaling pathways between cells. EVs derived from cell lines overexpressing STn were found to have the same glycosignature as the parent cells. EVs were isolated from different gastric cancer cell lines, including wild-type, COSMC gene knockout, ST6GalNAc1 overexpressing, and empty vector control. Immunofluorescence assays confirmed the presence of truncated O-glycans in the cells and their EVs. Analysis revealed that STn-positive cell lines released a higher number of EVs compared to STn-negative cell lines. Migration assays showed that recipient cells treated with STn-positive EVs had increased migration capacity, while STn-negative EVs had no effect. However, EV treatments did not affect cell proliferation. Proteomic analysis of EVs revealed the presence of proteins associated with the Notch signaling pathway. Notch pathway activation was confirmed by increased expression of Notch1 and its downstream target gene, SNAI2, in EV-treated cells. Overall, this study demonstrates that EVs enriched with truncated O-glycans can reprogram recipient gastric cancer cells, potentially through the activation of the Notch signaling pathway. These findings highlight the importance of EVs in facilitating communication within the tumor microenvironment and the role of truncated O-glycans in promoting cancer progression. Understanding the mechanisms underlying EV-mediated cell reprogramming could lead to the identification of new therapeutic targets for the treatment of gastric cancer. |
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| Autores principais: | José Miguel Teixeira Pires |
| Assunto: | Ciências médicas e da saúde Medical and Health sciences |
| Ano: | 2023 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso restrito |
| Instituição associada: | Universidade do Porto |
| Idioma: | inglês |
| Origem: | Repositório Aberto da Universidade do Porto |
| Resumo: | Glycans are important molecules involved in various cellular functions, particularly in cell-cell interactions at the cell membrane. In cancer, abnormal glycosylation disrupts cellular processes and contributes to increased malignancy. Specifically, truncated O-glycans like sialyl-Tn (STn) have been linked to invasiveness and poor prognosis in cancer patients. This study investigated how truncated O-glycans modulate gastric cancer cells through extracellular vesicles (EVs) carrying the same glycosignature. EVs are small structures released by cells that transport cargo and trigger signaling pathways between cells. EVs derived from cell lines overexpressing STn were found to have the same glycosignature as the parent cells. EVs were isolated from different gastric cancer cell lines, including wild-type, COSMC gene knockout, ST6GalNAc1 overexpressing, and empty vector control. Immunofluorescence assays confirmed the presence of truncated O-glycans in the cells and their EVs. Analysis revealed that STn-positive cell lines released a higher number of EVs compared to STn-negative cell lines. Migration assays showed that recipient cells treated with STn-positive EVs had increased migration capacity, while STn-negative EVs had no effect. However, EV treatments did not affect cell proliferation. Proteomic analysis of EVs revealed the presence of proteins associated with the Notch signaling pathway. Notch pathway activation was confirmed by increased expression of Notch1 and its downstream target gene, SNAI2, in EV-treated cells. Overall, this study demonstrates that EVs enriched with truncated O-glycans can reprogram recipient gastric cancer cells, potentially through the activation of the Notch signaling pathway. These findings highlight the importance of EVs in facilitating communication within the tumor microenvironment and the role of truncated O-glycans in promoting cancer progression. Understanding the mechanisms underlying EV-mediated cell reprogramming could lead to the identification of new therapeutic targets for the treatment of gastric cancer. |
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