Breast Cancer Cells in 3D Model Alters Their Sensitivity to Hormonal and Growth Factors

The purpose of this work was to study the formation and growth of mono- (3D) and heterogeneous (3D-2) spheroids composed of stromal and tumor cells that mimic three types of breast cancer: ER+/PR+, HER2+, and ER-/PR-/HER2 when spheroids are exposed to 17-β estradiol (E2) and TGF-β. Breast cancer cell lines MCF7, MDA-MB-231, SK-BR-3 and non-transformed BN120f fibroblasts were used to generate 3D and 3D-2 heterogeneous cultures. Uniform conditions for 3D culturing of all three breast-cancer cell lines are proposed that results in, proliferating spheroids. When tumor cells and healthy fibroblasts were mixed in a ratio of 1 : 4, the inner core of 3D-2 structures contained fibroblasts and the epithelial tumor cells formed outer layer of spheroids. The morphological analysis of spheroids showed that such co-cultivation of tumor and stromal cells in the 3D-2 model, produced more rounded and well-structured spheroids that is typical for self-organization into microtissue in comparison with 3D tumor cell model. It was found that E2 stimulated tumor cell proliferation in 3D and 3D-2 spheroids, regardless of that breast-cancer type these cells imitate. , while in 2D model, MDA-MB-231 cells were resistant to E2. In 3D models MDA-MB-231 cells lost, and SK-BR-3 cells acquired sensitivity to the pro-proliferative effect of TGF-β. Thus, it has been shown that 3D and 3D-2 cell models of breast cancer are an important tool to study the tumor progression and for testing new antitumor approaches, despite the existing 2D models.