Desenvolvimento e caracterização de um modelo de tumor de mama triplo-negativo a partir de células 4t1 em camundongos BALB/C

Abstract

Breast cancer is the most prevalent disease affecting women in Brazil and it is also the type of cancer with the highest mortality rate among Brazilian women. Cancer exhibits significant heterogeneity, both in terms of the intrinsic characteristics of each type and subtype, as well as the influences exerted by the tumor microenvironment and individual responses of each organ and/or individual. The process of tumor development, called carcinogenesis, involves a series of genetic and epigenetic cellular alterations that lead to uncontrolled cell growth and proliferation. In malignant tumors, cellular dedifferentiation, as well as the loss of function and the absence of clear boundaries, are characteristics related to the invasion of adjacent tissues and the occurrence of metastases. The metastatic process consists of the spread of tumor cells from the primary site, culminating in the colonization of a site for secondary tumor development. This process involves a cascade of events, from the loss of adhesion of cancer cells from the primary tumor to the colonization of a new tissue. Angiogenesis, which is the formation of new blood vessels to supply the tumor with nutrients and oxygen, is strongly stimulated when tumor growth reaches proportions that generate hypoxic regions, and it also facilitates the spread of tumor cells through the bloodstream. Among the subtypes of breast cancer, triple-negative breast cancer (TNBC) stands out due to the absence of ER, PR, and HER2 receptors, being considered one of the most aggressive types with the poorest prognosis. The present study aimed to develop an animal model to characterize triple-negative breast cancer originating from 4T1 cells in BALB/c mice. Through the development of this model, it was possible to identify cellular behaviors during the cultivation stage, as well as the primary tumor progression in animals, occurrence of metastases, and the histopathological characteristics of the tumors.