Characterization of cell lines derived from breast cancers and normal mammary tissues for the study of the intrinsic molecular subtypes

Abstract

Five molecular subtypes (luminal A, luminal B, HER2-enriched, basal-like, and claudin-low) with clinical implications exist in breast cancer. Here, we evaluated the molecular and phenotypic relationships of (1) a large in vitro panel of human breast cancer cell lines (BCCLs), human mammary fibroblasts (HMFs), and human mammary epithelial cells (HMECs); (2) in vivo breast tumors; (3) normal breast cell subpopulations; (4) human embryonic stem cells (hESCs); and (5) bone marrow-derived mesenchymal stem cells (hMSC). First, by integrating genomic data of 337 breast tumor samples with 93 cell lines we were able to identify all the intrinsic tumor subtypes in the cell lines, except for luminal A. Secondly, we observed that the cell lines recapitulate the differentiation hierarchy detected in the normal mammary gland, with claudin-low BCCLs and HMFs cells showing a stromal phenotype, HMECs showing a mammary stem cell/bipotent progenitor phenotype, basal-like cells showing a luminal progenitor phenotype, and luminal B cell lines showing a mature luminal phenotype. Thirdly, we identified basal-like and highly migratory claudin-low subpopulations of cells within a subset of triple-negative BCCLs (SUM149PT, HCC1143, and HCC38). Interestingly, both subpopulations within SUM149PT were enriched for tumor-initiating cells, but the basal-like subpopulation grew tumors faster than the claudin-low subpopulation. Finally, claudin-low BCCLs resembled the phenotype of hMSCs, whereas hESCs cells showed an epithelial phenotype without basal or luminal differentiation. The results presented here help to improve our understanding of the wide range of breast cancer cell line models through the appropriate pairing of cell lines with relevant in vivo tumor and normal cell counterparts.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-013-2743-3) contains supplementary material, which is available to authorized users.

Differential cytotoxic and radiosensitizing effects of silver nanoparticles on triple-negative breast cancer and non-triple-negative breast cells

“…23,40 Although the anticancer activity of AgNPs has been evaluated in several breast cancer cell lines in vitro 5,6 and in vivo, 7 differential effects of AgNPs in TNBC cells as compared to nontumorigenic breast cells have not been shown. Therefore, we evaluated the cytotoxicity of AgNPs in a panel of TNBC cell lines (MDA-MB-231, BT-549, and SUM-159), all of which exhibit features of claudin-low breast cancer, 41 in ER/PR positive, luminal A-like breast cancer cells (MCF-7), in noncancerous, transformed breast cells (MCF-10A), immortalized HMECs (184B5), 42 and in poststasis HMECs. 43 The cytotoxicity of AgNPs initially was evaluated by MTT assay following overnight exposure of cells to increasing concentrations of AgNPs (Figure 2A).…”

Prolactin receptor in breast cancer: marker for metastatic risk

“…SKBr3 and BT-483 were able to induce osteoclasts via conditioned media in a PRL-dependent manner. MCF7 cells have been identified as luminal breast cancer cells (Neve et al 2006, Kao et al 2009), luminal B in particular (Prat et al 2013). SKBr3 was identified as a luminal molecular subtype (Kao et al 2009), particularly luminal B with HER2 overexpression (Prat et al 2013).…”

“…MCF7 cells have been identified as luminal breast cancer cells (Neve et al 2006, Kao et al 2009), luminal B in particular (Prat et al 2013). SKBr3 was identified as a luminal molecular subtype (Kao et al 2009), particularly luminal B with HER2 overexpression (Prat et al 2013). BT-483 cells have been reported as luminal (Neve et al 2006), luminal B without HER2 expression (Kao et al 2009) or luminal B with HER2 overexpression (Prat et al 2013).…”

“…SKBr3 was identified as a luminal molecular subtype (Kao et al 2009), particularly luminal B with HER2 overexpression (Prat et al 2013). BT-483 cells have been reported as luminal (Neve et al 2006), luminal B without HER2 expression (Kao et al 2009) or luminal B with HER2 overexpression (Prat et al 2013). The differences in cellular response of MCF7 from other PRLR-positive cell lines may reflect alternate PRLR signaling pathways, different posttranscriptional processing of PRL-regulated targets such as sonic hedgehog (SHH) or a difference in qualitative response between the cell lines.…”

Endophilin A2 Promotes TNBC Cell Invasion and Tumor Metastasis

“…To study the function of Endo II in TNBC, we generated stable KDs of Endo II in two TNBC cell lines using a lentiviral system. It is worth noting that HCC 1806 cells represent basal-like, and MDA-MB-231 cells are basal B/claudin low (29). For each cell line, two separate shRNAs were tested (KD1, KD2), and these were compared with a control line expressing an NT shRNA.…”