Document Detail


Elucidating mechanical transition effects of invading cancer cells with a subnucleus-scaled microfluidic serial dimensional modulation device.
MedLine Citation:
PMID:  23212313     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mechanical boundaries that define and regulate biological processes, such as cell-cell junctions and dense extracellular matrix networks, exist throughout the physiological landscape. During metastasis, cancer cells are able to invade across these barriers and spread to distant tissues. While transgressing boundaries is a necessary step for distal colonies to form, little is known about interface effects on cell behavior during invasion. Here we introduce a device and metric to assess cell transition effects across mechanical barriers. Using MDA-MB-231 cells, a highly metastatic breast adenocarcinoma cell line, our results demonstrate that dimensional modulation in confined spaces with mechanical barriers smaller than the cell nucleus can induce distinct invasion phases and elongated morphological states. Further investigations on the impact of microtubule stabilization and drug resistance reveal that taxol-treated cells have reduced ability in invading across tight spaces and lose their super-diffusive migratory state and taxol-resistant cells exhibit asymmetric cell division at barrier interfaces. These results illustrate that subnucleus-scaled confinement modulation can play a distinctive role in inducing behavioral responses in invading cells and can help reveal the mechanical elements of non-proteolytic invasion.
Authors:
Michael Mak; Cynthia A Reinhart-King; David Erickson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Lab on a chip     Volume:  13     ISSN:  1473-0189     ISO Abbreviation:  Lab Chip     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-02     Completed Date:  2013-06-17     Revised Date:  2014-03-24    
Medline Journal Info:
Nlm Unique ID:  101128948     Medline TA:  Lab Chip     Country:  England    
Other Details:
Languages:  eng     Pagination:  340-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents, Phytogenic / pharmacology
Breast Neoplasms / genetics,  pathology
Cell Differentiation
Cell Line, Tumor
Cell Movement*
Cell Survival
Epithelial Cells / metabolism
Female
Humans
Microfluidic Analytical Techniques / instrumentation*
Microfluidics / methods*
Microtubules / metabolism
Neoplasm Invasiveness*
Neoplasm Metastasis / pathology
Neoplasms / metabolism
Paclitaxel / pharmacology
Grant Support
ID/Acronym/Agency:
U54 CA143876/CA/NCI NIH HHS; U54CA143876/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 33069-62-4/Paclitaxel
Comments/Corrections

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