PROTEOMIC CHARACTERIZATION OF THE EFFECT OF MANNOSE IN MURINE LINEAGES OF NORMAL AND TRANSFORMED MELANOCYTES

• Grant number: 23/05715-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2023
• End date: August 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Claudia Barbosa Ladeira de Campos
• Grantee: Luis Roberto Fonseca Lima
• Host Institution: Instituto de Ciência e Tecnologia (ICT). Universidade Federal de São Paulo (UNIFESP). Campus São José dos Campos. São José dos Campos , SP, Brazil

Abstract

The high energy demand observed during oncogenesis has important consequences for the metabolism of transformed cells, as well as significant impact on diagnostic methods and therapies associated with the treatment of neoplasms. Mannose is an epimer of glucose, absorbed by cells through the same transporters. Recent studies using tumor cell lines have shown that this hexose accumulates in cells in the form of the intermediate mannose-6-phosphate (M6P), due to the low expression of the enzyme phosphomannose isomerase (PMI), which converts M6P into fructose-6-phosphate (F6P), an intermediate of the glycolytic pathway. Recent data from our group indicate that normal murine melanocytes (Melan-a lineage) are sensitive to mannose. In addition, we observed that the conditioned medium from normal cells sensitizes metastatic tumor cells of the B16-F10 lineage (normally insensitive to this hexose). In this context, the main objective of this project is to evaluate the effects of mannose administration on the cellular proteome of normal and tumor melanocyte murine lineages (Melan-a and B16-F10, respectively), as well as to perform proteomic characterization of the conditioned medium from the mannose-sensitive lineage (Melan-a). We hope to correlate the results obtained with possible relevant biological pathways to the oncogenic process. From a therapeutic point of view, the results obtained will allow the elucidation of fundamental molecular aspects that could support the development of clinical intervention strategies using this hexose (mannose) associated with therapies already used for the treatment of melanoma.