Evaluation of galectin-3 role in the adaptative process of tumor cells in response of inflammatory immune response and chemotherapeutic selective pressures in the tumoral microenvironment

• Grant number: 08/11513-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): April 01, 2009
• Effective date (End): April 30, 2012
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Roger Chammas
• Grantee: Camila Maria Longo Machado
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 98/14247-6 - Center for Research on Cell-Based Therapy, AP.CEPID

Abstract

The number of articles that establish a relationship between inflammation and success in tumorigenesis is increasing. Many evidences from a clinical point of view show that inflammatory cytokines lead to a pro-tumoral microenvironment. Additionally, some transcription factors such as NFkB link the innate and adaptative immune response inflammation to tumorigenesis and cancer.After innate immune response activation, restraint of huge amounts of tumor cells occurs in the microenvironment, leading to the tumor cells death, which can activate the adaptive immune response. That way, the persistent stimulation of the immune system can increase the production of inflammatory mediators, the differentiation of cells that promote angiogenesis and modifications of the microenvironment in favor of the evolutionary success of tumor cells. The immune response may act as a struggle for tumoral cells existence, which generates tumor phenotypes that retains positive characteristic that has been favored by selective process, such as chemoresistance. In addition, chemotherapy can itself generate an exacerbated antigenicity by the death of tumor cells that enhance the activation of the immune system and develop an evolutionary press favoring the generation of a tumor phenotype fully adapted to the microenvironment conditions.Thus, the identification of molecules that perform multifunctional roles and are present both in the tumor and in the microenvironment can help oncologists to design more specific and effective therapies against these tumor cells. Galectin-3 appears to be as a molecule with important roles in physiological functions such as in the development and activation of the immune system as well as in the tumor success. In our laboratory, we have demonstrated that galectin-3 plays a role favoring tumor adaptation in microenvironment hypoxic conditions and, furthermore, there were histological evidences of the probable role of galectin-3 in angiogenesis. However, it is not yet fully established the exact role of galectin-3 in the tumor microenvironment such as in the modulation of the inflammatory innate and adaptive immune response pathways, or in the profile of induced cytokines. Besides the role of galectin-3 in cells differentiation to compose new blood vessels in tumor sites still poorly understood.Therefore, this project aims at defining the role of galectin-3 in the evolutionary adaptation of the tumor microenvironment, the phenomenon of angiogenesis, with respect to the inflammatory immune response and cellular front of the selective pressure of drug cisplatin.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LONGO MACHADO, CAMILA MARIA; SOUSA ANDRADE, LUCIANA NOGUEIRA; TEIXEIRA, VERONICA RODRIGUES; COSTA, FABRICIO FALCONI; MELO, CAMILA MORAIS; DOS SANTOS, SOFIA NASCIMENTO; NONOGAKI, SUELY; LIU, FU-TONG; BERNARDES, EMERSON SOARES; CAMARGO, ANAMARIA ARANHA; et al. Galectin-3 disruption impaired tumoral angiogenesis by reducing VEGF secretion from TGF beta 1-induced macrophages. CANCER MEDICINE, v. 3, n. 2, p. 201-214, APR 2014. (98/14247-6, 08/11513-0)