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

用于量化乳腺癌标本转移倾向的微流体分析

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作者:Christopher L Yankaskas, Keyata N Thompson, Colin D Paul, Michele I Vitolo, Panagiotis Mistriotis, Ankit Mahendra, Vivek K Bajpai, Daniel J Shea, Kristen M Manto, Andreas C Chai, Navin Varadarajan, Aikaterini Kontrogianni-Konstantopoulos, Stuart S Martin, Konstantinos Konstantopoulos

Abstract

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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