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Effect of mesenchymal stem cells on the growth of canine and murine melanomas: in vitro and in vivo studies

Grant number: 17/17237-4
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2018
Effective date (End): November 30, 2020
Field of knowledge:Agronomical Sciences - Veterinary Medicine - Animal Pathology
Principal Investigator:Maria Lucia Zaidan Dagli
Grantee:Taticia Lieh Ikeda
Home Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Melanoma is the most aggressive form among skin neoplasia and difficult to treat if not diagnosed early. At the tumor microenvironment, mesenchymal stem cells (MSC) perform an important role on several tumor subpopulations profile and development. These cells possess an innate tropism for tumor tissues, which allows the employment of MSC for therapeutic delivery of anticancer drugs. However, using MSC as therapeutic tools for cancer treatment is still controversial due to the dual effect that these cells show on tumor growth. The inhibitory effect of MSC can be obtained by cell polarization to a pro-inflammatory phenotype. Thus, this study aims to evaluate the effect of naïve and pro-inflammatory MSC on the development of tumor cells and the ability of these cells to modulate the immune system within the tumor microenvironment. To this end, murine and canine MSC will be polarized with lipopolysaccharides (LPS) or polyinosinic:polycytidylic acid (poly I:C) and cultivated in vitro with melanoma cells, in the presence of T cells or not. We will evaluate tumor growth during 2D and 3D culture, cell viability, migration and invasion potential, T cells subsets and cytokine and growth factors profile. In vivo studies will also be performed to analyze MSC ability to home to the tumor site and their influence on the tumor microenvironment. Therefore, we hope to achieve a safer method to use MSC as therapeutic tool for cancer treatment.