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Incretin signal in tumor progression in the experimental model of Colorectal Cancer associated with Colitis

Grant number: 20/14388-4
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): April 01, 2021
Effective date (End): March 31, 2024
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal researcher:Alvaro Pacheco e Silva Filho
Grantee:Eloisa Martins da Silva
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated research grant:17/05264-7 - Cell metabolism, microbiota and immune system: new paradigms in renal diseases physiopathology, AP.TEM

Abstract

Currently, is estimated that the number of Cancer cases and deaths resulting from it is 18.1 and 9.6 million, respectively. The Colorectal Cancer (CRC) is the 3rd type with major incidence. The Colorectal Cancer associated with Colitis is a subtype of CRC related to intestinal inflammatory interaction, difficult treatment and high mortality index. The intestinal epithelial is formed by immune cells (lymphocytes T and B, macrophages and dendritic cells) and no-immune cells, such as enterocytes, enteroendocrine cells, tuft cells, globlet cells and Paneth cells. In approximal 35% of CRC, the enteroendocrine cells (EEC) differentiation is detect. They represent about 1% of epithelial, synthesize and secrete hormones peptides with stimulation, and are crucial for intestinal inflammation. The hormones produced for EEC make part of a class called Incretins (GLP-1 and GIP), both with insulinotropic effects, used in patients with type II diabetes therapies. Currently, the pancreas, liver and gut Cancer progression are associated with incretin hormones. In animals models, receptor agonists from one of an incretin produced by EECs (GLP-1R) works such as intestinal tumorigenic regulatory and another hormone from the same group, the GIP, was highlighted as a possible-like stimulator of cells proliferation in CRC. However, wasn't evident the influence of receptor agonist from hormones GLP-1 and GIP and enzyme DPP4 inhibitors in CRC development and progression. Thus, our hypothesis is that the agonist of hormones GLP-1 and GIP and DPP4 inhibitors modulate the antitumor response and, consequently, influence the CRC progression. Preliminary results show that there is a significant difference in genes related to incretin and the DPP4 enzyme in a study with CRC patients, which points to a significant role of these genes in the disease progression that should be better elucidated. Therefore, in this study we search for clarify the importance of hormones GLP-1 and GIP and the DPP4 enzyme in development of Colorectal Cancer associated with Colitis and to get innovative data which could help in understanding the disease and improve patients therapy. (AU)