Evaluation of telocytes' role in the reactive stroma formation in a model of induced carcinogenesis in the gerbil female prostate (Meriones unguiculatus)

• Grant number: 19/14201-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): March 01, 2020
• Effective date (End): July 31, 2023
• Field of knowledge: Biological Sciences - Morphology - Histology
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Sebastião Roberto Taboga
• Grantee: Juliana dos Santos Maldarine
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

The prostate is not a gland exclusively of males, but it is also present in females of diverse species, including in a portion of the women. The Mongolian gerbil (Meriones unguiculatus) is a rodent species in which the prostate is present in most females and there are indications, both in this species and in humans, that it can suffer from the same pathologies that affect the prostate of males, such as protatites and adenocarcinomas. However, there is not yet a model of carcinogenesis induction for female prostate. In addition, the complexity of the female prostate increases when we consider that it also has telocytes in its stroma. Telocytes are newly described interstitial cells that are present in several organs and are known to play a role in the organization of the tissue in the prostate and myocardium, and also secrete growth and differentiation factors and may have several functions in other organs. However, the correlations that these cells may have with tumor tissues, such as cancer, are unknown. The objective of this study is to produce a method of induction of prostate cancer in females and to evaluate the presence and possible function of telocytes in prostate stroma in a model of carcinogenesis induced by methylnitrosourea, testosterone and estradiol (MNU-T -E2) in the gerbil. It is aimed to obtain a method of induction of cancer in the prostate of females which takes into account the dependence of estradiol, besides verifying the repercussions that the telocytes can present in the formation and maintenace of the reactive stroma of the prostate, as well as an additional treatment with an antiestrogen, tamoxifen, will be performed to evaluate the responsiveness of these cells in this context. To do so, we will use techniques of immunohistochemistry, immunofluorescence, transmission electron microscopy, cell cultures, and conditioned media. The developments of this project may be important for the understanding of still unknown mechanisms related to the establishment of the tumor microenvironment, which makes it promising both in terms of pure science and in terms of the search for new therapeutic targets for cancer. (AU)