Effect of mesenchymal tumor cells on the growth of murine and canine melanoma growth: in vitro and in vivo studies

• Grant number: 18/02402-2
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2018
• End date: February 28, 2021
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Maria Lucia Zaidan Dagli
• Grantee: Maria Lucia Zaidan Dagli
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Melanoma is the most aggressive form of skin tumors and difficult to treat if not diagnosed early. In the tumor microenvironment, mesenchymal stem cells (MTC) play an important role on the profile and development of the various subpopulations present in the tumor. The tropism of these cells by tumor tissues enables the use of CTMs as delivery vehicles for antitumor therapeutic agents. However, its use as a therapeutic tool in the treatment of tumors is still controversial, considering that MTCs may either contribute to or inhibit neoplastic growth. It has already been demonstrated that the antitumor effect of CTM can be obtained by polarizing these cells into a proinflammatory phenotype. Thus, this project aims to evaluate the effect of naïve and pro-inflammatory MTCs on the development of tumor cells and their ability to modulate the immune system of the tumor microenvironment. For this purpose, murine and canine CTMs will be polarized with lipopolysaccharides (LPS) or polynucleic acid-polycytidylic acid (poly I: C) and cultured in vitro with melanoma cells in the presence or not of T cells. Growth of tumor cells during monolayer (2D) or three-dimensional (3D) culture, cell viability, migration and invasiveness, proportion of T cell populations and cytokine profile and growth factors. In vivo tests will also be performed to assess the ability of MTCs to migrate to the tumor and its influence on the tumor microenvironment. With this study, it is therefore expected to make the use of MTCs safer in the treatment of tumors. (AU)