The challenge of predicting which patients with breast cancer will develop metastases leads to the overtreatment of patients with benign disease and to the inadequate treatment of aggressive cancers. Here, we report the development and testing of a microfluidic assay that quantifies the abundance and proliferative index of migratory cells in breast cancer specimens, for the assessment of their metastatic propensity and for the rapid screening of potential antimetastatic therapeutics. On the basis of the key roles of cell motility and proliferation in cancer metastasis, the device accurately predicts the metastatic potential of breast cancer cell lines and of patient-derived xenografts. Compared with unsorted cancer cells, highly motile cells isolated by the device exhibited similar tumourigenic potential but markedly increased metastatic propensity in vivo. RNA sequencing of the highly motile cells revealed an enrichment of motility-related and survival-related genes. The approach might be developed into a companion assay for the prediction of metastasis in patients and for the selection of effective therapeutic regimens.
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The main data supporting the results of this study are available within the paper and its Supplementary Information files. Source data for the figures in this study are available from the corresponding author upon reasonable request. RNA sequencing data are available at the National Center for Biotechnology Information Gene Expression Omnibus, under accession number GSE128313.
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This line of research was supported by the National Cancer Institute through grants R01-CA183804 (K.K., A.K.-K., S.S.M.), R01-CA216855 (K.K.), R01-CA154624 (S.S.M.), R01-CA174385 (N.V.) and K01-CA166576 (M.I.V.), as well as by CPRIT RP180466 (N.V.), MRA Award 509800 (N.V.), CDMRP CA160591 (N.V.) and Department of Defense grant W81XWH-17-1-0246 (V.K.B.). M.I.V. was also supported by a Research Scholar Grant, RSG-18-028-01-CSM, from the American Cancer Society.
The PTEN−/− cells are licensed to Horizon Discovery Ltd (Cambridge, UK). M.I.V receives compensation for the sale of these cells. MAqCI is the subject of US Utility Patent applications 15/780,768 and 14/906,055.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary figures, tables and video legends.
Genes upregulated by migratory compared with unsorted MDA-MB-231 cells.
Genes downregulated by migratory compared with unsorted MDA-MB-231 cells.
Definition of migratory and non-migratory cells in MAqCI.
Non-migratory MCF7 breast cancer cells in MAqCI.
Migration of breast cancer cells obtained from patient-derived xenografts in MAqCI.
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Yankaskas, C.L., Thompson, K.N., Paul, C.D. et al. A microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens. Nat Biomed Eng 3, 452–465 (2019). https://doi.org/10.1038/s41551-019-0400-9
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