MAGICIAM: a MAcrophaGe Immunomodulatory-delivery system to prevent Cancer Invasion And Metastasis

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Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression

Publication . Pinto, Ana Teresa; Machado, Ana Beatriz; Osório, Hugo; Pinto, Marta Laranjeiro; Vitorino, Rui; Justino, Gonçalo; Santa, Cátia; Castro, Flávia; Cruz, Tânia; Rodrigues, Carla; Lima, Jorge; Sousa, José Luís R.; Cardoso, Ana Patrícia; Figueira, Rita; Monteiro, Armanda; Marques, Margarida; Manadas, Bruno; Pauwels, Jarne; Gevaert, Kris; Mareel, Marc; Rocha, Sónia; Duarte, Tiago; Oliveira, Maria José; DQ - Departamento de Química; LAQV@REQUIMTE; MDPI - Multidisciplinary Digital Publishing Institute

Purpose: To identify a molecular signature of macrophages exposed to clinically relevant ionizing radiation (IR) doses, mirroring radiotherapy sessions. Methods: Human monocyte-derived macrophages were exposed to 2 Gy/ fraction/ day for 5 days, mimicking one week of cancer patient’s radiotherapy. Protein expression profile by proteomics was performed. Results: A gene ontology analysis revealed that radiation-induced protein changes are associated with metabolic alterations, which were further supported by a reduction of both cellular ATP levels and glucose uptake. Most of the radiation-induced deregulated targets exhibited a decreased expression, as was the case of cathepsin D, a lysosomal protease associated with cell death, which was validated by Western blot. We also found that irradiated macrophages exhibited an increased expression of the transferrin receptor 1 (TfR1), which is responsible for the uptake of transferrin-bound iron. TfR1 upregulation was also found in tumor-associated mouse macrophages upon tumor irradiation. In vitro irradiated macrophages also presented a trend for increased divalent metal transporter 1 (DMT1), which transports iron from the endosome to the cytosol, and a significant increase in iron release. Conclusions: Irradiated macrophages present lower ATP levels and glucose uptake, and exhibit decreased cathepsin D expression, while increasing TfR1 expression and altering iron metabolism.

2022-12-30Artigo científico

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Entidade financiadora

Fundação para a Ciência e a Tecnologia

Programa de financiamento

9471 - RIDTI

Número da atribuição

PTDC/BTM-SAL/31859/2017