Abstract
Metastasis is the most common cause of cancer-related death and, as such, there is an urgent need to discover new therapies to treat metastasized cancers. Cancer cell lines are widely-used models to study cancer biology and evaluate drug candidates. However, it is still unknown whether they adequately recapitulate the disease in patients. The recent accumulation of large-scale genomic data in cell lines, mouse models, and patient tissue samples provides an unprecedented opportunity to evaluate the suitability of cancer cell lines as models for metastatic cancer research. Through comprehensively comparing the genomic profiles of 57 breast cancer cell lines with those of metastatic breast cancer samples, we found their substantial genomic differences. We also identified cell lines that more closely resemble different subtypes of metastatic breast cancer. However, we found none of the currently established Basal-like cell lines sufficiently resemble the samples of Basal-like metastatic breast cancer, a subtype of high interest in therapeutic discovery. Further analysis of mutation, copy number variation and gene expression data suggested that MDAMB231, the most commonly used triple negative cell line, had little genomic similarity with Basal-like metastatic breast cancer samples. Our work demonstrates an urgent need of cell lines that more closely resemble Basal-like metastatic breast cancer samples, and could guide cell line selection in other metastasis-related translational research.
Why was this study done?> Cancer cell lines are commonly used as models to understand cancer metastasis and test drug candidates preclinically, while the degree to which these cell lines accurately reflect metastatic breast cancer in vivo is not well established. We leveraged large-scale genomic data to comprehensively evaluate breast cancer cell lines as models for metastatic breast cancer.
What did the researchers do and find?> The comparison of genetic profiles between breast cancer cell lines and metastatic breast cancer samples revealed that cell lines poorly recapitulated the somatic mutation spectrum of metastatic breast cancer samples, while copy-number variation profiles were considerably consistent.
> Gene expression correlation analysis identified cell lines which closely resembled metastatic breast cancer samples of LuminalA/LuminalB/Her2-enriched subtypes, but none of the currently established cell lines resembles Basal-like metastatic breast cancer samples. Specifically, the most commonly used triple negative cell line MDAMB231 had low genomic similarity with metastatic breast cancer samples from patients.
> Global transcriptome analysis revealed striking differences between breast cancer cell lines and metastatic breast cancer samples.
What do these findings mean?> These findings indicate that we should keep in mind the large genomic disparity between breast cancer cell lines and metastatic breast cancer samples when using cell lines in translational research, and we are still in urgent need of new cell lines (or other preclinical models) for Basal-like metastatic breast cancer research.