Action mechanisms of deflamin in the treatment of colorectal cancer

• Autor(a) principal: Silva, Sara Miguel Jesus
• Data de Publicação: 2022
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.1/18802
• topic: Deflamin; Matrix metalloproteinases; Zebrafish; 3D spheroids.; Domínio/Área Científica::Ciências Médicas::Outras Ciências Médicas

CRC is the third most common cancer in the world and the second leading cause of death worldwide, being its mortality associated with the dissemination to distant organs. For cancer to become invasive and metastatic it is necessary that a remodeling of the extracellular matrix occurs being the matrix metalloproteases (MMPs) the main molecules involved in this process. Since MMPs have major implications for migratory and angiogenic processes, promoting greater tumor malignancy, they are strong candidates to targeted therapies in order to delay malignant progression. Deflamin is a 17 kDa oligomeric protein extracted from the white lupine seeds (Lupinus albus) with anti-inflammatory and MMP-2 and 9 inhibitory functions. Deflamin has been shown to induce an improvement of the colonic mucosa and inhibit the migratory activity in CRC cell lines. In in vivo studies previously developed in our lab, deflamin was shown to exert an anti-tumor and pro-apoptotic activity. In this context, my work aimed to clarify the mechanism of deflamin action using 3D and in vivo zebrafish xenotransplant models. Overall, my results demonstrate that deflamin has an inhibitory role of the tumoral invasive process without significantly affecting proliferation of CRC cell lines. Regarding in vivo analysis, I found a trend towards less vessel infiltration in deflamin treated groups. Deflamin has also shown to be effective in reducing collagen degradation in the tumor microenvironment of zebrafish treated animals, indicating less extracellular matrix remodeling. These results agree with results obtained previously in CRC lines and in vivo assays. Therefore, increasing our knowledge on the role of deflamin for CRC development has the potential to reveal a new nutritional therapeutic approach, with major implications for the health and well-being of CRC patients.