High-Throughput Cellular Heterogeneity Analysis in Cell Migration at the Single-Cell Level

Mengli Zhou; Yushu Ma; Chun-Cheng Chiang; Edwin C Rock; Kathryn E Luker; Gary D Luker; Yu-Chih Chen

doi:10.1002/smll.202206754

High-Throughput Cellular Heterogeneity Analysis in Cell Migration at the Single-Cell Level

Small. 2023 Feb;19(6):e2206754. doi: 10.1002/smll.202206754. Epub 2022 Nov 30.

Authors

Mengli Zhou^{1

2

3}, Yushu Ma^{1

2}, Chun-Cheng Chiang^{1

2}, Edwin C Rock⁴, Kathryn E Luker⁵, Gary D Luker^{5

6

7}, Yu-Chih Chen^{1

2

4

8}

Affiliations

¹ UPMC Hillman Cancer Center, University of Pittsburgh, 5115 Centre Ave, Pittsburgh, PA, 15232, USA.
² Department of Computational and Systems Biology, University of Pittsburgh, 3420 Forbes Avenue, Pittsburgh, PA, 15260, USA.
³ Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
⁴ Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, 3700 O'Hara Street, Pittsburgh, PA, 15260, USA.
⁵ Center for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA.
⁶ Department of Microbiology and Immunology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA.
⁷ Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel, Blvd, Ann Arbor, MI, 48109-2099, USA.
⁸ CMU-Pitt Ph.D. Program in Computational Biology, University of Pittsburgh, 3420 Forbes Avenue, Pittsburgh, PA, 15260, USA.

Abstract

Cancer cell migration represents an essential step toward metastasis and cancer deaths. However, conventional drug discovery focuses on cytotoxic and growth-inhibiting compounds rather than inhibitors of migration. Drug screening assays generally measure the average response of many cells, masking distinct cell populations that drive metastasis and resist treatments. Here, this work presents a high-throughput microfluidic cell migration platform that coordinates robotic liquid handling and computer vision for rapidly quantifying individual cellular motility. Using this innovative technology, 172 compounds were tested and a surprisingly low correlation between migration and growth inhibition was found. Notably, many compounds were found to inhibit migration of most cells while leaving fast-moving subpopulations unaffected. This work further pinpoints synergistic drug combinations, including Bortezomib and Danirixin, to stop fast-moving cells. To explain the observed cell behaviors, single-cell morphological and molecular analysis were performed. These studies establish a novel technology to identify promising migration inhibitors for cancer treatment and relevant applications.

Keywords: breast cancer; cell migration; image processing; metastasis; microfluidics; single-cell analysis.

Publication types

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

MeSH terms

Cell Line, Tumor
Cell Movement
Drug Discovery*
High-Throughput Screening Assays
Microfluidics*
Single-Cell Analysis

Abstract

Publication types

MeSH terms

Grants and funding