Tryptophan metabolism in melanomas: What do the microenvironment cells tell us?

• Grant number: 10/18477-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2011
• End date: February 28, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Ana Campa
• Grantee: Renan Orsati Clara
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Tryptophan (TRP) metabolism occurs by kynurenine pathway (KYN pathway) and by serotoninergic pathway (SER pathway). KYN pathway generates kynurenine (KYN) and a lot of secondary products and, when it is conducted by indoleamine 2,3 dioxygenase enzyme (IDO), it contributes to tolerance phenomena and tumor cells immune escape. SER pathway produces serotonin (SER) which can generate melatonin (MLT) and other metabolites with immunomodulatory effects. In cancer regards, there are evidences that these compounds can control tumor growth. Giving the great importance on biochemical pathways of TRP metabolism in tumors, the initial aim of this project is to develop, standardize and validate new protocols for identification and quantification of metabolites from TRP metabolic pathways, especially tending to protocols that will allow us to obtain a large number of synchronic information and sensitivity. Subsequently, we will identify the different TRP metabolites in human melanoma tumor lineages, melanocytes and clinical samples of melanoma. In tumor lineages we will evaluate IFN-³ and 1-methyl-tryptophan (1-MT) effects; respectively an inductor and a competitive inhibitor of IDO. In clinical samples, KYN and SER pathways metabolites will be correlated to tumor development stage and to treatment response. From the data collected in this study, we intend to recognize what is the impact of one pathway over the other and the TRP metabolism on the neoplasic process, especially, in melanomas.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CLARA, RENAN ORSATI; ASSMANN, NADINE; RAMOS MORENO, ANA CAROLINA; COIMBRA, JANINE BAPTISTA; NURENBERGER, NADINE; DETTMER-WILDE, KATJA; OEFNER, PETER JOSEF; CAMPA, ANA. Melanocytes are more responsive to IFN-gamma and produce higher amounts of kynurenine than melanoma cells. Biological Chemistry, v. 397, n. 1, p. 85-90, JAN 2016. (10/18477-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CLARA, Renan Orsati. Tryptophan metabolism in melanomas:what do microenvironment cells can say?. 2015. Doctoral Thesis - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.