Development and cytotoxic response of two proliferative MDAMB-231 and non-proliferative SUM1315 three-dimensional cell culture models of triple-negative basal-like breast cancer cell lines

Abstract

Triple-Negative Basal-Like tumors, representing 15 to 20% of breast cancers, are very aggressive and with poor prognosis. Targeted therapies have been developed extensively in preclinical and clinical studies to open the way for new treatment strategies. The present study has focused on developing 3D cell cultures from SUM1315 and MDA-MB-231, two triple-negative basal-like (TNBL) breast cancer cell lines, using the liquid overlay technique. Extracellular matrix concentration, cell density, proliferation, cell viability, topology and ultrastructure parameters were determined. The results showed that for both cell lines, the best conditioning regimen for compact and homogeneous spheroid formation was to use 1000 cells per well and 2% Geltrex®. This conditioning regimen highlighted two 3D cell models: non-proliferative SUM1315 spheroids and proliferative MDA-MB-231 spheroids. In both cell lines, the comparison of 2D vs 3D cell culture viability in the presence of increasing concentrations of chemotherapeutic agents i.e. cisplatin, docetaxel and epirubicin, showed that spheroids were clearly less sensitive than monolayer cell cultures. Moreover, a proliferative or non-proliferative 3D cell line property would enable determination of cytotoxic and/or cytostatic drug activity. 3D cell culture could be an excellent tool in addition to the arsenal of techniques currently used in preclinical studies.