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Article

Deciphering Hydrodynamic and Drug-Resistant Behaviors of Metastatic EMT Breast Cancer Cells Moving in a Constricted Microcapillary

1
Department of Mechanical Engineering, Indian Institute of Technology Guwahati, Guwahati 781 039, India
2
Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781 039, India
3
Centre for BioSystems Science and Engineering, Indian Institute of Science Bangalore, Bangalore 560 012, India
4
Department of Mechanical Engineering, Indian Institute of Technology Kanpur, Kanpur 208 016, India
*
Author to whom correspondence should be addressed.
The authors contributed equally to this article.
J. Clin. Med. 2019, 8(8), 1194; https://doi.org/10.3390/jcm8081194
Received: 5 July 2019 / Revised: 3 August 2019 / Accepted: 7 August 2019 / Published: 9 August 2019
Epithelial to mesenchymal transition (EMT) induces cell migration, invasion, and drug resistance, and consequently, contributes to cancer metastasis and disease aggressiveness. This study attempted to address crucial biological parameters to correlate EMT and drug-treated cancer cells traversing through microcapillaries, reminiscent of metastatic conditions. MDA-MB-468 breast cancer cells induced to undergo EMT by treatment with 20 ng/mL of epidermal growth factor (EGF) were initially passed through several blockages and then through a constricted microchannel, mimicking the flow of invasive metastatic cells through constricted blood microcapillaries. EMT cells acquired enhanced migratory properties and retained 50% viability, even after migration through wells 10–15 μm in size and a constricted passage of 7 μm and 150 μm in length at a constant flow rate of 50 μL/h. The hydrodynamic properties revealed cellular deformation with a deformation index, average transit velocity, and entry time of 2.45, 12.3 mm/s, and 31,000 μs, respectively for a cell of average diameter 19 μm passing through one of the 7 μm constricted sections. Interestingly, cells collected at the channel outlet regained epithelial character, undergoing reverse transition (mesenchymal to epithelial transition, MET) in the absence of EGF. Remarkably, real-time polymerase chain reaction (PCR) analysis confirmed increases of 2- and 2.7-fold in the vimentin and fibronectin expression in EMT cells, respectively; however, their expression reduced to basal level in the MET cells. A scratch assay revealed the pronounced migratory nature of EMT cells compared with MET cells. Furthermore, the number of colonies formed from EMT cells and paclitaxel-treated EMT cells after passing through a constriction were found to be 95 ± 10 and 79 ± 4, respectively, confirming that the EMT cells were more drug resistant with a concomitant two-fold higher expression of the multi-drug resistance (MDR1) gene. Our results highlight the hydrodynamic and drug-evading properties of cells that have undergone an EMT, when passed through a constricted microcapillary that mimics their journey in blood circulation. View Full-Text
Keywords: metastasis; constricted microchannel; hydrodynamic parameters; breast cancer cells; epithelial to mesenchymal transition; EMT; mesenchymal to epithelial transition; MET; cell viability metastasis; constricted microchannel; hydrodynamic parameters; breast cancer cells; epithelial to mesenchymal transition; EMT; mesenchymal to epithelial transition; MET; cell viability
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MDPI and ACS Style

Nath, B.; Bidkar, A.P.; Kumar, V.; Dalal, A.; Jolly, M.K.; Ghosh, S.S.; Biswas, G. Deciphering Hydrodynamic and Drug-Resistant Behaviors of Metastatic EMT Breast Cancer Cells Moving in a Constricted Microcapillary. J. Clin. Med. 2019, 8, 1194. https://doi.org/10.3390/jcm8081194

AMA Style

Nath B, Bidkar AP, Kumar V, Dalal A, Jolly MK, Ghosh SS, Biswas G. Deciphering Hydrodynamic and Drug-Resistant Behaviors of Metastatic EMT Breast Cancer Cells Moving in a Constricted Microcapillary. Journal of Clinical Medicine. 2019; 8(8):1194. https://doi.org/10.3390/jcm8081194

Chicago/Turabian Style

Nath, Binita, Anil P. Bidkar, Vikash Kumar, Amaresh Dalal, Mohit K. Jolly, Siddhartha S. Ghosh, and Gautam Biswas. 2019. "Deciphering Hydrodynamic and Drug-Resistant Behaviors of Metastatic EMT Breast Cancer Cells Moving in a Constricted Microcapillary" Journal of Clinical Medicine 8, no. 8: 1194. https://doi.org/10.3390/jcm8081194

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