A microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens

• Published in: Nature biomedical engineering Vol. 3; no. 6; pp. 452 - 465
• Main Authors: Yankaskas, Christopher L., Thompson, Keyata N., Paul, Colin D., Vitolo, Michele I., Mistriotis, Panagiotis, Mahendra, Ankit, Bajpai, Vivek K., Shea, Daniel J., Manto, Kristen M., Chai, Andreas C., Varadarajan, Navin, Kontrogianni-Konstantopoulos, Aikaterini, Martin, Stuart S., Konstantopoulos, Konstantinos
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2019; Nature Publishing Group
• Subjects: 13/51; 13/62; 14/5; 14/63; 38/22; 38/77; 38/91; 631/114/2413; 631/61/350/877; 631/67/1347; 631/67/322; 64/60; Animals; Assaying; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedicine; Breast cancer; Breast Neoplasms - pathology; Carcinogenesis - pathology; Cell Line, Tumor; Cell migration; Cell Movement; Cell proliferation; Cell survival; Clinical Trials as Topic; Drug development; Epithelial Cells - pathology; Female; Gene sequencing; Genotype; Humans; In vivo methods and tests; Metastases; Metastasis; Mice, Nude; Microfluidics; Microfluidics - methods; Motility; Mutation - genetics; Neoplasm Invasiveness; Neoplasm Metastasis; Phenotype; Ribonucleic acid; RNA; Signal Transduction; Tumor cell lines; Xenograft Model Antitumor Assays; Xenografts; Xenotransplantation
• ISSN: 2157-846X; 2157-846X
• DOI: 10.1038/s41551-019-0400-9

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. A microfluidic assay predicts the metastatic potential of breast cancer specimens by quantifying the abundance and proliferative index of the migratory cells within them.