MacrOral_CESPU_2017: Relating Monocarboxylate Transporters (MCTs) Expression to Macrophage Polarization in Oral Squamous Cell Carcinoma.
admin-cespu
Principal Investigator:
Luis Miguel Moutinho da Silva Monteiro (luis.monteiro@iucs.cespu.pt)
Leader Institution:
CESPU
Research Team:
Hassan Bousbaa, Odília Queirós, Patrícia Silva, Leonor Delgado, Andrea Cunha, Ana Henriques, José Barbas do Amaral, Maria José Oliveira, Fátima Baltazar
Funding entity:
CESPU
Budget:
6.000,00 €
Period covered:
2017-2018
Abstract:
Recently, tumor-derived lactic acid (or lactate), a byproduct of aerobic and anaerobic glycolysis, was demonstrated to shift murine macrophage polarization towards M2 phenotype, the macrophage type that, in contrary to the tumoricidal M1 type, boosts tumor growth, angiogenesis, immunosuppression, and metastasis. Here, we propose to study whether such relationship also applies to human cancer, using oral squamous cell carcinoma (OSCC) as a model. Firstly, we will evaluate the expression of monocarboxylate transporters MCT1 and MCT4 (lactate transporters) in OSCC biopsies. As OSCC cases overexpressing MCT1/MCT4 are expected to transport lactate in the stroma, we predict M2 macrophages to be the prevalent phenotype in these tumors. Thus, OSCC will also be screened for M1 and M2 macrophages markers by immunohistochemistry, and correlation between macrophage polarization and MCT1,4 expression evaluated. Secondly, we propose to test the relationship between MCT1,4 expression and M2 macrophage differentiation in an in vitro model system using cancer cell lines.
Recently, tumor-derived lactic acid (or lactate), a byproduct of aerobic and anaerobic glycolysis, was demonstrated to shift murine macrophage polarization towards M2 phenotype, the macrophage type that, in contrary to the tumoricidal M1 type, boosts tumor growth, angiogenesis, immunosuppression, and metastasis. Here, we propose to study whether such relationship also applies to human cancer, using oral squamous cell carcinoma (OSCC) as a model. Firstly, we will evaluate the expression of monocarboxylate transporters MCT1 and MCT4 (lactate transporters) in OSCC biopsies. As OSCC cases overexpressing MCT1/MCT4 are expected to transport lactate in the stroma, we predict M2 macrophages to be the prevalent phenotype in these tumors. Thus, OSCC will also be screened for M1 and M2 macrophages markers by immunohistochemistry, and correlation between macrophage polarization and MCT1,4 expression evaluated. Secondly, we propose to test the relationship between MCT1,4 expression and M2 macrophage differentiation in an in vitro model system using cancer cell lines.
Project area: