Journal
ONCOTARGET
Volume 7, Issue 9, Pages 10486-10497Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.7251
Keywords
circulating tumor cells; microtentacles; breast cancer; microfluidics; polyelectrolyte multilayers
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Funding
- Era of Hope Scholar Award from the Department of Defense [BC100675]
- NSF CAREER Award [1351688]
- NCI [F30-CA196075]
- NIH [T32 AI089621]
- American Association of Pharmaceutical Scientists Foundation
- Damon Runyon Foundation [DRR3415]
- Alliance for Cancer Gene Therapy [15051543]
- Melanoma Research Alliance [348963]
- [R01-CA154624]
- [R01-CA124704]
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [1351688] Funding Source: National Science Foundation
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Free-floating tumor cells located in the blood of cancer patients, known as circulating tumor cells (CTCs), have become key targets for studying metastasis. However, effective strategies to study the free-floating behavior of tumor cells in vitro have been a major barrier limiting the understanding of the functional properties of CTCs. Upon extracellular-matrix (ECM) detachment, breast tumor cells form tubulin-based protrusions known as microtentacles (McTNs) that play a role in the aggregation and re-attachment of tumor cells to increase their metastatic efficiency. In this study, we have designed a strategy to spatially immobilize ECM-detached tumor cells while maintaining their free-floating character. We use polyelectrolyte multilayers deposited on microfluidic substrates to prevent tumor cell adhesion and the addition of lipid moieties to tether tumor cells to these surfaces through interactions with the cell membranes. This coating remains optically clear, allowing capture of high-resolution images and videos of McTNs on viable free-floating cells. In addition, we show that tethering allows for the real-time analysis of McTN dynamics on individual tumor cells and in response to tubulin-targeting drugs. The ability to image detached tumor cells can vastly enhance our understanding of CTCs under conditions that better recapitulate the microenvironments they encounter during metastasis.
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