A high-throughput microfabricated platform for rapid quantification of metastatic potential
Assays that measure morphology, proliferation, motility, deformability, and migration are used to study the invasiveness of cancer cells. However, native invasive potential of cells may be hidden from these contextual metrics because they depend on culture conditions. We created a micropatterned chip that mimics the native environmental conditions, quantifies the invasive potential of tumor cells, and improves our understanding of the malignancy signatures. Unlike conventional assays, which rely on indirect measurements of metastatic potential, our method uses three-dimensional microchannels to measure the basal native invasiveness without chemoattractants or microfluidics. No change in cell death or proliferation is observed on our chips. Using six cancer cell lines, we show that our system is more sensitive than other motility-based assays, measures of nuclear deformability, or cell morphometrics. In addition to quantifying metastatic potential, our platform can distinguish between motility and invasiveness, help study molecular mechanisms of invasion, and screen for targeted therapeutics.
Authors
- Miran Yoo (ORCID: https://orcid.org/0000-0003-0031-1362)
- James Hone (ORCID: https://orcid.org/0000-0002-8084-3301)
- Evren U. Azeloglu (ORCID: https://orcid.org/0000-0001-6137-109X)
- G. Luca Gusella (ORCID: https://orcid.org/0000-0001-8385-8704)
- Jonathan C. Haydak (ORCID: https://orcid.org/0000-0002-9091-8987)
- Abora Ettela
- Teng‐Leong Chew (ORCID: https://orcid.org/0000-0002-3139-7560)
- Alan D. Stern (ORCID: https://orcid.org/0000-0002-7772-642X)
- Emily J. Gallagher (ORCID: https://orcid.org/0000-0002-7920-8474)
- Chad M. Hobson (ORCID: https://orcid.org/0000-0003-3033-5728)
- Smiti Bhattacharya (ORCID: https://orcid.org/0000-0002-5965-571X)
Institutions
- Howard Hughes Medical Institute (US)
- Janelia Research Campus (US)
- Imaging Center (US)
- Columbia University (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Science Advances
- Published
- 2024-08-16
- DOI
- https://doi.org/10.1126/sciadv.adk0015
- Citations
- 6
- Primary Topic
- Cellular Mechanics and Interactions
- Type
- article
- Field-Weighted Citation Impact
- 1.96
Funders
- U.S. Department of Defense