Immunohistochemical evaluation of LOX, LOXL2 and HIF1-alpha expression in canine mammary tumors

• Grant number: 20/12789-1
• Support type: Scholarships in Brazil - Master
• Effective date (Start): January 01, 2021
• Effective date (End): March 31, 2023
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal researcher: Ricardo de Francisco Strefezzi
• Grantee: Jessika Daniel Urel
• Home Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
• Associated scholarship(s): 21/14519-4 - Evaluation of lox and HIF1-alpha expression in hypoxia and normoxia using canine mammary tumor cell culture, BE.EP.MS

Abstract

Cancer is the most common cause of death in dogs. Mammary tumors present great histological heterogeneity, which makes the establishment an accurate prognosis difficult. The extracellular matrix (ECM) is one of the main components of the tumor microenvironment, as well as vascularization and cells of the immune system. The ECM may influence tumor cell proliferation and inhibit or stimulate angiogenesis. Collagen, an important component of ECM, is crosslinked by the lysyl oxidase (LOX) and other members of this enzyme family. Hypoxia induces tumoral and stromal expression of LOX through the Hypoxia Inducible Factor 1 alpha (HIF1-alpha). Moreover, the overexpression of LOX and LOXL2 are closely related to worse prognosis in cancer patients. The aim of the present research is to characterize the immunohistochemical expression of LOX, LOXL2 and HIF1-alpha as prognostic markers for canine mammary neoplasms, comparing the results with histological types, mortality due to the tumor and post-surgical survival. We hypothesize that higher expressions of LOX, LOX2 and HIF1-alpha are related to more anaplastic tumors, shorter post-surgical survival and higher mortality due to the disease. This work may provide useful information for novel prognostic markers and for further research on therapeutic targets in canine mammary tumors. (AU)