The Differences in MDA-MB-231 triple-negative breast cancer cell sub-lines

Abstract

Introduction Triple-negative breast cancer (TNBC) is one of the most aggressive and highly heterogeneous tumors with morphologically distinct subtypes [1]. Currently, there is no molecular-based targeted therapy for TNBC. The complicated treatment of TNBC can be associated with tumor heterogeneity and tumors are highly resistant to chemotherapy and it is related to the phenotypic heterogeneity of tumor cell populations. Scientists found that in genetically homogeneous cell populations, phenotypic heterogeneity is frequently observed in in vitro cell cultures even in a controlled environment [2]. Identifying the differences between populations and their response to anticancer drugs could help to predict the tumor resistance to chemotherapy [3]. The aim of our study was to characterize phenotypically different sub-lines derived from the commercial MDA-MB-231 cell line. Materials and methods Sub-lines isolation was performed by multiple dilutions of the cell suspension in a 96-well microplate. Sub-lines have been characterized by the expression of the CD133 receptor (by immunofluorescence staining), their susceptibility and 2D cell interaction influence to anticancer drugs doxorubicin (DOX) and paclitaxel (PTX) (by MTT assay), the ability to migrate (by wound healing assay). Results The expression of the CD133 receptor was more than 31% higher in the sub-line F5 compared to the MDA-MB-231 cell line. The susceptibility of cell sub-lines to the tested anticancer drugs was different. Sub-line H2 was the most resistant to DOX more than 39% (EC50 value after 72 hours was 158.7 ± 33.3 μM, whereas EC50 value for MDA-MB-231 cell line was 140.0 ± 23.2 μM). All sub-lines were from 2 to 4 times more resistant to PTX compared to the parent MDA-MB-231 cell line. The results from the cell migration study showed that the migration rate of sub-lines D8, F7, G5, and H2 was from 20 to 40% higher in comparison to MDA-MB-231 line. Different combinations of sub-lines and their