TY - JOUR
T1 - A microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens
AU - Yankaskas, Christopher L.
AU - Thompson, Keyata N.
AU - Paul, Colin D.
AU - Vitolo, Michele I.
AU - Mistriotis, Panagiotis
AU - Mahendra, Ankit
AU - Bajpai, Vivek K.
AU - Shea, Daniel J.
AU - Manto, Kristen M.
AU - Chai, Andreas C.
AU - Varadarajan, Navin
AU - Kontrogianni-Konstantopoulos, Aikaterini
AU - Martin, Stuart S.
AU - Konstantopoulos, Konstantinos
N1 - Funding Information:
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.
Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - 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.
AB - 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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U2 - 10.1038/s41551-019-0400-9
DO - 10.1038/s41551-019-0400-9
M3 - Article
C2 - 31061459
AN - SCOPUS:85065324254
SN - 2157-846X
VL - 3
SP - 452
EP - 465
JO - Nature biomedical engineering
JF - Nature biomedical engineering
IS - 6
ER -