Role of kinin receptors in tumor-associated-macrophages & lung cancer cells

• Grant number: 17/00386-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2017
• End date: December 31, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Isis Cristina Corrêa Do Nascimento
• Grantee: Isabella Elias Yonezawa Ogusuku
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cancer is postulated to be a disease of abnormal cell division controlled by a series of genetic mutations. Lung cancer is the most commonly diagnosed type of cancer as well as the leading cause of cancer-related deaths worldwide. Inflammation, a hallmark of cancer that has been widely studied in the last decades, supplies tumor cells with sufficient factors that are important for their survival and progression. Inflammatory cells, especially tumor-associated macrophages (TAMs), are recruited by tumor cells and infiltrate tumor tissues. Recent investigations have shown that TAMs can promote tumor development and progression by angiogenesis and suppression of the adaptive immunity. In order to perform their biological functions, macrophages must first be activated through several cytokines. Not only cytokines determinate the polarization of the macrophages into M1 or M2 subtypes, but the polarized subtypes also produce characteristic group of cytokines in response. Kallikreins are serine proteases that produce kinin peptides from kininogen substrates. Kinins are generated within inflammatory tissue microenvironments, where they exert diverse functions, including cell proliferation, cell migration and leukocyte activation. The functions of the kallikrein-kinin system (KKS) are mediated through the activation of both subtypes of the kinin receptors: the B2 and B1 receptors. Thus, the aim of this project is to investigate the role of kinin receptors in TAMs as well as in lung cancer cells. Therefore, a NSCLC A549 cell line and macrophages obtained from monocytic THP-1 cells will be cultured as model of study. (AU)