Células MCF-7 como modelo 3D no estudo de câncer de mama humano.

Abstract

Do Amaral JB. MCF-7 cells as a 3D model in the study of human breast cancer. [Ph. D. thesis (Cell and Tissue Biology)]. Sao Paulo: Instituto de Ciencias Biomedicas da Universidade de Sao Paulo; 2010. Cell culture is characterized by maintaining live cells in the laboratory regardless of the organism in which they originated. This technique has contributed to better understanding of molecular cell mechanisms, permitting important scientific advances, for example, concerning vaccine production and tumor cell biology. Three-dimensional (3D) cell culture initially derived from commonly used cell cultures (monolayer cell cultures). As a particularity, a 3D cell culture permits cells to explore the three dimensions of the space thereby increasing cell-cell interactions, as well as interaction with the environment. When grown in this system, cells form structures known as multicelullar spheroids. The interior of these spheroids present cell heterogeneity, microenvironment formation and different exposure to factors, such as nutrients and oxygen. Owing to the fact that these characteristics are very similar to those of in vivo avascular tumors, 3D cell culture advanced in various research lines, thus becoming a widely used model in radiology and chemotherapy essays. In studies related to breast cancer biology, spheroids are becoming widely used in the aim to comprehend luminal space morphogenesis. In this context, the objective here was to develop a 3D culture model that made it possible to analyze spheroid formation using 3 characteristics that have not yet been described in the literature: without addition of basement membrane mimetic, use of tumor cell lines and, lastly, cell exposure for periods longer than 30 days in 3D cell culture. We showed that, in the aforementioned conditions, MCF-7 cells reorganize themselves in tubular and acinar structures. In both situations, lumen formation was accompanied by the establishment of a layer of polarized cells, an arrangement that is very similar to that of breast glands. The presented results suggest the existence of an MCF cell line population not completely committed to the tumor phenotype. When maintained as differentiated, MCF-7 cell spheroids can be a new model for studies regarding lumen formation, thereby exploring the role of diiferent pathways, such as those related to cell apoptosis, autophagy, differentiation and survival.