Abstract
Cancer cell metastasis is a major factor in cancer-related mortality. During the process of metastasis, cancer cells exhibit migratory phenotypes and invade through pores in the dense extracellular matrix. However, the characterization of morphological and subcellular features of cells in similar migratory phenotypes and the effects of geometric confinement on cell morphodynamics are not well understood. Here, we investigate the phenotypes of highly aggressive MDA-MB-231 cells in single cell and cell doublet (an initial and simplified collective state) forms in confined microenvironments. We group phenotypically similar single cells and cell doublets and characterize related morphological and subcellular features. We further detect two distinct migratory phenotypes, fluctuating and non-fluctuating, within the fast migrating single cell group. In addition, we demonstrate an increase in the number of protrusions formed at the leading edge of cells after invasion through geometric confinement. Finally, we track the short and long term effects of varied degrees of confinement on protrusion formation. Overall, our findings elucidate the underlying morphological and subcellular features associated with different single cell and cell doublet phenotypes and the impact of invasion through confined geometry on cell behavior.
Highlights
Cancer cell metastasis is a major factor in cancer-related mortality
The process of cancer metastasis is understood as a series of cell transport events, beginning with cells invading through physical constraints of the primary site, followed by transendothelial migration, and culminating in the colonization of a secondary t issue[1,8]
A recent study has shown that the metastatic potential of cancer cells in vivo may be related to the morphologies of those cells on a 2D s ubstrate[10]
Summary
During the process of metastasis, cancer cells exhibit migratory phenotypes and invade through pores in the dense extracellular matrix. The characterization of morphological and subcellular features of cells in similar migratory phenotypes and the effects of geometric confinement on cell morphodynamics are not well understood. Cancer metastasis can involve a single cell or a small tumor cluster interacting and migrating c ollectively[15,16,17,18]. The analysis of cell doublets may serve as an important simplified type of collective migration beneficial to understanding the migratory behaviors of small tumor clusters. We previously developed a microfluidic multi-staged serial invasion channels (MUSIC) device platform with parallelized constriction channels in series that mimic the constrictive barriers in the microenvironment This device has been used to measure cancer cell deformation and relaxation, drug treatment’s impact on cancer cell invasiveness, e tc[19,20,21]. We previously developed a custom fluorescence analysis approach
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
