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The role of HSP70/HSP90 in tumor derived-exosome in cachetic patients

Grant number: 18/13394-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): October 01, 2018
Effective date (End): September 30, 2020
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Principal Investigator:Marilia Cerqueira Leite Seelaender
Grantee:Rodrigo da Silva Camargo de Sousa
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cachexia associated with cancer is a multifactorial syndrome characterized mainly by severe weight loss, accompanied by great metabolic imbalance. It is believed to result from the interaction between the host and tumor, inducing systemic inflammation. Understanding the relationship between the tumor microenvironment and inflammation is fundamental for the discovery of effective markers for diagnosis and reversal of the syndrome. Cellular communication between the tumor and other tissues may occur by inflammatory mediators such as cytokines, immune cells, or also by microvesicles, which are known as exosomes and can be transferred to remote sites to regulate the function of distant cells and affect the processes of receptor cells, promoting the interaction between several cells in the tumor microenvironment. Exosomes are small extracellular vesicles derived from multivesicular endosomes, secreted by all cells and present in all body fluids and play an important role in the development of cancer. A recent study with tumor-inoculated Wistar rats that develop cachexia has shown that cellular communication between tumor and peripheral tissues occurs through the exosomes and carries within them the heat shock proteins (HSP70 / HSP90), which when increased in the circulation , has the function of accentuating the muscular degradation. Thus, the objective of this work is to analyze the protein profile of HSP70 and HSP90 in the tumor derived exosomes of patients with cachexia and to correlate these results with the inflammatory profile expressed in the patients' tumor microenvironment. The study will involve 20 patients diagnosed with colon and rectum adenocarcinoma, later distributed into two groups, following the classification criteria of cachexia adopted by the international consensus (Evans et al, 2008): Cancer without cachexia (WSC = 10) and Cancer with cachexia (CC = 10).