Expression and function of kinin receptors in tumor cells and in cells of the immune system

• Grant number: 11/15562-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2012
• End date: February 28, 2014
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Elaine Guadelupe Rodrigues
• Grantee: Mariana Ferrazzo Souza
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 10/51423-0 - Bioactive peptides and peptidases: biological and immunobiological activities in infectious diseases and cancer, AP.TEM

Abstract

Melanoma originates from melanocytes (melanin-producing cells), and is a tumor with high metastatic potential and low effective available treatments (chemotherapy and radiotherapy), all of them showing severe undesirable side effects. Breast cancer is the second prevalent cancer worldwide and the most prevalent among women, being also difficult to control and treat. Tumor development can induce innate and adaptive immune responses that recognize specific tumor antigens however, due to the induction of a predominant Th2 response, the protective Th1 type antitumor response is impaired. Immunotherapeutic alternatives that induce Th1 responses have been evaluated as adjuvants to conventional treatments. During tumor progression, generation and cleavage of factors, such as kinins, by proteolytic enzymes can modulate tumor development. Bradykinin was implicated in tumor angiogenesis, but cells from immune system also expressed kinin receptors, with several of them being activated by kinins and agonists, suggesting that kinins can modulate the immune response. Kinin receptors have also been identified in tumor cells, and in some cases, their activation interferes with the proliferation, invasion / migration, and also with secretion of molecules by tumor cells. The role of kinins originated in the tumor microenvironment by proteases secreted locally is not known, and it is unclear whether these peptides can modulate the antitumor immune response. The objective of this project is to verify the expression of kinin receptors in murine B16F10 melanoma and 4T1 breast carcinoma cells, and whether their activation can induce a response in these tumor cells. Additionally, another goal of this project is to evaluate the ability of kinins to modify the non-protective Th2 predominant antitumor immune response to a Th1 antitumor protective response.