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

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

doi:10.1038/s41551-019-0400-9

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

Nat Biomed Eng. 2019 Jun;3(6):452-465. doi: 10.1038/s41551-019-0400-9. Epub 2019 May 6.

Authors

Christopher L Yankaskas^{1

2}, Keyata N Thompson³, Colin D Paul^{1

2}, Michele I Vitolo^{3

4

5}, Panagiotis Mistriotis^{1

2}, Ankit Mahendra⁶, Vivek K Bajpai⁷, Daniel J Shea¹, Kristen M Manto¹, Andreas C Chai¹, Navin Varadarajan⁶, Aikaterini Kontrogianni-Konstantopoulos^{3

8}, Stuart S Martin^{3

4

5}, Konstantinos Konstantopoulos^{9

10

11

12}

Affiliations

¹ Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA.
² Johns Hopkins Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, MD, USA.
³ Marlene and Stewart Greenebaum National Cancer Institute Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
⁴ Graduate Program in Molecular Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
⁵ Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
⁶ Department of Chemical and Biomolecular Engineering, University of Houston, Houston, TX, USA.
⁷ Department of Chemical and Systems Biology, Stanford University, Stanford, CA, USA.
⁸ Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA.
⁹ Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA. konstant@jhu.edu.
¹⁰ Johns Hopkins Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, MD, USA. konstant@jhu.edu.
¹¹ Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD, USA. konstant@jhu.edu.
¹² Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. konstant@jhu.edu.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Breast Neoplasms / pathology*
Carcinogenesis / pathology
Cell Line, Tumor
Cell Movement
Clinical Trials as Topic
Epithelial Cells / pathology
Female
Genotype
Humans
Mice, Nude
Microfluidics / methods*
Mutation / genetics
Neoplasm Invasiveness
Neoplasm Metastasis
Phenotype
Signal Transduction
Xenograft Model Antitumor Assays

Abstract

Publication types

MeSH terms

Grants and funding