Evaluation of the role of toll-like receptor2 (TLR2) in the development of cancer in obese animals

Author(s)

Juliana Alves Camargo

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2014-12-08

Examining board members

José Barreto Campello Carvalheira; André Almeida Schenka; Marcos Brasilino de Carvalho

• Advisor: José Barreto Campello Carvalheira

Abstract

Among the diseases with the highest incidence of death in American countries, obesity and cancer are very important, and today we can say that these are connected. Studies have shown a strong association between obesity and some types of cancer, such as colon and breast cancer. Higher adiposity result in the worse prognosis for these diseases. However, the reasons why obesity increase the risk of these cancers have not been completely elucidated. Several hypotheses have been raised, including the association of adiposity with subclinical inflammatory response, in which excess of adipose tissue results in high levels of inflammatory cytokines, contributing to the initiation and progression of cancer. The inflammation generated by adiposity stimulates the activation of inflammatory proteins such as JNK and IKK. These proteins activate transcription factors such as NF-kB, Stat-3 and AP-1, that control the expression of pro-inflammatory genes such as TNF and IL-6. Recently our group demonstrated that the TNFa is an important molecule in the promotion of colon tumors in obese animals. We evaluated in this study the role of TLR2, as receptor that is already established the role in the genesis of subclinical inflammation found in obesity, colon and breast cancer mediated by obesity. Our results demonstrated that the reduction of TLR2 activity protects the animals from development of breast, colon, and skin cancer. Interestingly, like the animal control, animals in high fat diet also showed attenuation of the development of cancer. Mechanistically, inhibition of TLR2 reduces the activity of IKK and protects the development of cancer through repression of the release of IL-6 and TNF pro-inflammatory cytokines. Accordingly, this study demonstrated that TLR2 is crucial for the development of different types of cancer in both animals control and fed with high fat diet (AU)

• FAPESP's process: 11/04116-8 - Evaluation of the TLR2 function in breast cancer development in obesity animal models
• Grantee: Juliana Alves de Camargo
• Support Opportunities: Scholarships in Brazil - Master