Breast Cancer Cell Line Classification and Its Relevance with Breast Tumor Subtyping

Abstract

Breast cancer cell lines have been widely used for breast cancer modelling which encompasses a panel of diseases with distinct phenotypical associations. Though cell lines provide unlimited homogenous materials for tumor studies and are relatively easy to culture, they are known to accumulate mutations duringthe initial establishment and subsequent series of cultivations. Thus, whether breast cancer cell line heterogeneity reflects that of carcinoma remains an important issue to resolve before drawing any reliable conclusion at the tumor level using cell lines. Inconsistent nomenclatures used for breast cancer cell line subtyping and the different number of subtypes grouped for cell lines and tumors make their direct matching elusive. By analyzing the molecular features of 92 breast cancer cell lines as documented by different literatures, we categorize 84 cell lines into 5 groups to be consistent with breast tumor classification. After combing through these cell lines, we summarized the molecular features, genetically and epigenetically, of each subtype, and manually documented 10 cell lines lacking explicit information on subtyping. Nine cell lines, either found inconsistent on their primary molecular features from different studies or being contaminated at the origin, are not suggested as the first choice for experimental use. We conclude that breast tumor cell lines, though having a high mutational frequency with many uncertainties and could not fully capture breast cancer heterogeneity, are feasible but crude models for tumors of the same subtype. New cell lines with enriched interferon regulated genes need to be established to enlarge the coverage of cell lines on tumor heterogeneity.

Keywords: breast cancer; cell line; molecular feature; subtyping.

Figure 1

Comparison of the current subtyping schemes between breast cancer cell lines and tumors. According to the status of ER, PR, HER2, breast cancer is classified as luminal A, luminal B, HER2 positive, and triple negative, where triple negative tumors can be further differentiated into at least basal, claudin-low, MBC (metaplastic breast cancer) and interferon-rich. The current literatures, in general, do not differentiate luminal cell lines; HER2 positive cell lines are diffused into luminal B and triple negative cells, and named luminal-HER2+ and ER-negative-HER2+, respectively; and triple negative cells are called the 'Basal' subtype, with basal A and basal B being further differentiated to represent the basal tumors and claudin-low and/or MBC tumors, respectively. The morphological features of the subtypes in tumors and cell lines accord well, with luminal tumors having better prognosis and luminal cell lines less aggressive than that in triple negative tumors and cell lines.