Heterotypic culture: The Cross-Talking between epithelial tumor cells, mammary stroma, macrophages and platelets in breast cancer: the release of proteolytic enzymes and signaling of Toll-like receptors

• Grant number: 12/19851-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2013
• End date: April 30, 2016
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Manoel João Batista Castello Girão
• Grantee: Sheila Siqueira Andrade
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Breast cancer is a multifactorial disease heterotypic which for a long time researchers have tried to extract its complexity with cultivation of epithelial cells. This system enabled the advancement of genetics and molecular biology of cancer. However, cultivation of single immortalized breast epithelial cells is insufficient to mimic the tumor microenvironment. There is evidence that in breast carcinomas, 90% of the cells present in the tumor mass, are not neoplastic, stromal cells include resident adipocytes and fibroblasts, a wide range of recruited hematopoietic cells, and newly formed blood vessels with their associated cells. Dynamic and reciprocal communication between epithelial and stromal compartments occurs during breast cancer progression. The stromal cells, such as cancer associated fibroblasts or tumor-associated macrophages, promote tumor progression by secreting growth factors, chemokines, promigratory extracellular matrix components and proteolytic enzymes.In this sense, culture heterotypic basically formed by epithelial cells, mammary stroma, macrophages and platelets exhibit a better alternative for investigation of biochemical signals associated with the proteolytic enzymes and trophic factors agonists of Toll-like receptors.This project aims to: 1) the characterization of cells and tissues extracted from biopsies of patients with and without breast cancer. 2) and subsequently identifying the proteolytic enzymes that are secreted interaction with these cells via library of substrates frets, 3) after identification of enzymes and substrates will proceed with the evaluation of platelet activation by these enzymes; in assays invasion and proliferation. 4) Finally, target the activation of toll-like receptors in epithelial cells and platelets, the culture medium of culture heterotypic between fibroblasts and adipocytes.

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)

BONAZZA, CAMILA; ANDRADE, SHEILA SIQUEIRA; SUMIKAWA, JOANA TOMOMI; BATISTA, FABRICIO PEREIRA; PAREDES-GAMERO, EDGAR J.; GIRAO, MANOEL J. B. C.; OLIVA, MARIA LUIZA V.; CASTRO, RODRIGO AQUINO. Primary Human Uterine Leiomyoma Cell Culture Quality Control: Some Properties of Myometrial Cells Cultured under Serum Deprivation Conditions in the Presence of Ovarian Steroids. PLoS One, v. 11, n. 7, JUL 8 2016. (12/19851-8, 09/53766-5, 12/19780-3)

ANDRADE, SHEILA SIQUEIRA; GOUVEA, IURI ESTRADA; SILVA, MARIANA CRISTINA C.; CASTRO, ELOISA DOGNANI; DE PAULA, CLAUDIA A. A.; OKAMOTO, DEBORA; OLIVEIRA, LILIAN; PERES, GIOVANI BRAVIN; OTTAIANO, TATIANA; FACINA, GIL; et al. Cathepsin K induces platelet dysfunction and affects cell signaling in breast cancer - molecularly distinct behavior of cathepsin K in breast cancer. BMC CANCER, v. 16, MAR 1 2016. (12/19851-8, 09/53766-5, 12/19780-3)

ANDRADE, SHEILA SIQUEIRA; SUMIKAWA, JOANA TOMOMI; CASTRO, ELOISA DOGNANI; BATISTA, FABRICIO PEREIRA; PAREDES-GAMERO, EDGAR; OLIVEIRA, LILIAN CAROLINA; GUERRA, IZABEL MONASTERIO; PERES, GIOVANI BRAVIN; CAVALHEIRO, RENAN PELLUZZI; JULIANO, LUIZ; et al. Interface between breast cancer cells and the tumor microenvironment using platelet-rich plasma to promote tumor angiogenesis - influence of platelets and fibrin bundles on the behavior of breast tumor cells. ONCOTARGET, v. 8, n. 10, p. 16851-16874, 2017. (12/19851-8, 09/53766-5, 12/19780-3)