TY - JOUR

T1 - Breast Cancer Cells in 3D Model Alters Their Sensitivity to Hormonal and Growth Factors

AU - Nushtaeva, A. A.

AU - Savinkova, M. M.

AU - Ermakov, M. S.

AU - Varlamov, M. E.

AU - Novak, D. D.

AU - Richter, Vladimir A.

AU - Koval, O. A.

N1 - FUNDING: This work was supported by the Russian Science Foundation, project no. 20-74-10039. BN120f cell cultivation was carried out within the framework of Russian StateFunded Budget Project, grant number 121030200173-6.

PY - 2022/12/1

Y1 - 2022/12/1

N2 - 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.

AB - 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.

KW - 17-β estradiol

KW - 3D cell cultures

KW - breast cancer

KW - cell lines

KW - epidermal growth-factor receptor type 2 (HER2)

KW - fibroblasts

KW - transforming growth factor β

KW - tumor cells

UR - https://www.scopus.com/inward/record.url?eid=2-s2.0-85144392981&partnerID=40&md5=783005e7563ad3e1d95ea19ca5aed9b0

UR - https://www.mendeley.com/catalogue/353c61b3-b80e-3d2b-a69c-19edcb970ba3/

U2 - 10.1134/S1990519X22060050

DO - 10.1134/S1990519X22060050

M3 - Article

VL - 16

SP - 555

EP - 567

JO - Cell and Tissue Biology

JF - Cell and Tissue Biology

SN - 1990-519X

IS - 6

ER -