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Contribution of mesenchymal stem cells to tumor development

Grant number: 11/10001-9
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2011
Effective date (End): February 28, 2015
Field of knowledge:Interdisciplinary Subjects
Principal Investigator:Oswaldo Keith Okamoto
Grantee:Carolina de Oliveira Rodini
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

This research project focuses on the involvement of mesenchymal stem cells (MSCs) in the development of malignant tumors in the central nervous system. Besides migration to sites of injury, MSCs also display tropism to tumors, being recruited to its microenvironment where they may contribute to the tumor stroma and niche. This process is still poorly understood and its clarification should help the better understanding of the molecular and cellular mechanisms underlying cancer progression. MSCs are known to express the TGFB1 gene encoding a multifunctional cytokine (TGFbeta1). In addition to an immunomodulatory activity, TGFbeta1 may also regulate the proliferation and migration of tumor cells, and is involved in the epithelial-mesenchymal transition, thereby contributing to tumor invasion, metastatic spread, and acquisition of tumor resistance to therapy. In the central nervous system, TGFbeta1 contributes to the development of glioblastoma multiforme (GBM), the most frequent and malignant primary brain tumor. GBM is associated with poor clinical prognosis and no effective treatments are currently available for GBM patients. Considering recent evidences of a MSC-like phenotype in cells comprising human GBM specimens, we hypothesize that MSCs could be recruited by GBM, favoring its development.In this context, the aim of this project is to investigate the relevance of TGFbeta1 produced by MSCs to the tumorigenic properties of GBM, including its effects on tumor cell proliferation, migration and invasion. This project expects to increase knowledge about mechanisms underlying the development of human malignant gliomas, in particular the pro-tumorigenic contribution of MSCs through paracrine effects within the tumor niche.

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)
GONCALVES DA SILVA, PATRICIA BENITES; TEIXEIRA DOS SANTOS, MARCIA CRISTINA; RODINI, CAROLINA OLIVEIRA; KAID, CAROLINI; LEITE PEREIRA, MARCIA CRISTINA; FURUKAWA, GABRIELA; GIMENES DA CRUZ, DANIEL SANZIO; GOLDFEDER, MAURICIO BARBUGIANI; REILY ROCHA, CLARISSA RIBEIRO; ROSENBERG, CARLA; OKAMOTO, OSWALDO KEITH. High OCT4A levels drive tumorigenicity and metastatic potential of medulloblastoma cells. ONCOTARGET, v. 8, n. 12, p. 19192-19204, 2017. Web of Science Citations: 1.
TEIXEIRA SANTOS, MARCIA CRISTINA; GONCALVES SILVA, PATRICIA BENITES; RODINI, CAROLINA OLIVEIRA; FURUKAWA, GABRIELA; MARCO ANTONIO, DAVID SANTOS; ZANOTTO-FILHO, ALFEU; MOREIRA, JOSE C. F.; OKAMOTO, OSWALDO KEITH. Embryonic Stem Cell-Related Protein L1TD1 Is Required for Cell Viability, Neurosphere Formation, and Chemoresistance in Medulloblastoma. STEM CELLS AND DEVELOPMENT, v. 24, n. 22, p. 2700-2708, NOV 15 2015. Web of Science Citations: 3.
KAID, CAROLINI; SILVA, PATRICIA B. G.; CORTEZ, BEATRIZ A.; RODINI, CAROLINA O.; SEMEDO-KURIKI, PATRICIA; OKAMOTO, OSWALDO K. miR-367 promotes proliferation and stem-like traits in medulloblastoma cells. Cancer Science, v. 106, n. 9, p. 1188-1195, SEP 2015. Web of Science Citations: 22.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
RODINI, Carolina de Oliveira. Contribution of mesenchymal stem cells to the tumorigenic properties of human glioblastoma cells. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Biociências São Paulo.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.