Chitinase 3-like-1 and fibronectin in the cargo of extracellular vesicles shed by human macrophages influence pancreatic cancer cellular response to gemcitabine
The work recently published in the journal “Cancer Letters” by Cristina Xavier et al., in the scope of her post-doctoral research at the Cancer Drug Resistance Group, i3S, demonstrated the impact of Extracellular Vesicles released by macrophages on the response of pancreatic cancer cells to a chemotherapeutic agent. This work results from a collaboration with the Tumor and Microenvironment Interactions Group of i3S, the Experimental Pathology and Therapeutics Group of IPO-Porto and the Genetic Diversity Group of i3S.
Bronchoalveolar lavage is routinely collected during bronchoscopy for cytology analysis in the diagnostic of lung cancer. Due to low sensitivity of this method, early-stage cancers are undetected, lowering the treatment success. In this study, we analysed extracellular vesicles isolated from bronchoalveolar lavage of lung cancer suspects by mass spectrometry-based proteomics. The protein composition of bronchoalveolar lavage extracellular vesicles of late-stage cancer showed a higher proteome complexity associated with mortality within the two year follow-up period.
O lavado broncoalveolar é recolhido através de broncoscopia para análise citológica no diagnóstico de cancro do pulmão. Devido à baixa sensibilidade do método, os tumores em estadio inicial não são detetados, o que diminui o sucesso do tratamento. Neste estudo, analisámos por espectrometria de massa vesículas extracelulares isoladas a partir do lavado broncoalveolar de indivíduos suspeitos de cancro do pulmão.
Joana Maia1,2, Andreia Hanada Otake1,3, Juliana Poças4,5,6, Ana Sofia Carvalho7, Hans Christian Beck8, Ana Magalhães4,5, Rune Matthiesen7, Maria Carolina Strano Moraes1 and Bruno Costa-Silva1
1-Champalimaud Centre for the Unknown, Champalimaud Foundation, Lisbon, Portugal
2-Graduate Program in Areas of Basic and Applied Biology, University of Porto, Porto, Portugal
O cancro de pâncreas é a quarta principal causa de mortes relacionadas ao cancro no mundo, apresentando uma taxa de sobrevida de 5 anos de cerca de 6% e uma taxa de sobrevida média de cerca de 6 meses. Entre os cancros pancreáticos, o adenocarcinoma ductal pancreático (CP) é o tipo mais comum e é responsável por mais de 90% dos casos. Uma combinação de fatores leva ao mau prognóstico do CP, incluindo dificuldades na deteção da doença em estágio inicial, seu alto potencial metastático e sua resistência às terapias convencionais.
Identification of the metabolic alterations associated with the multidrug resistant phenotype in cancer and their intercellular transfer mediated by extracellular vesicles
Cancer multidrug resistance (MDR) is a major cause of therapeutic failure in cancer. MDR is mainly due to the overexpression of drug efflux pumps, such as P-glycoprotein (P-gp). Besides overexpression of drug efflux pumps, other molecular mechanisms are involved in the MDR phenotype, including metabolic alterations. Indeed, recent studies showed that it is possible to revert the MDR phenotype by inhibition of glycolysis with specific modulators.