Document Detail


Gene expression profiles in 3D tumor analogs indicate compressive strain differentially enhances metastatic potential.
MedLine Citation:
PMID:  20559731     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Non-physiological mechanobiological stimuli typically occur in tumors and are considered to promote cancer spreading. Non-fluid related pressure (solid stress), which arises as tumors grow against adjacent tissues, is among the least studied endogenous stimuli due to challenges in replicating the in vivo environment. To this end, the novel devices well-pressor and the videomicroscopy-compatible optic-pressor were developed to exert precise compressive strain on cells in 3D gels in absence of other mechanical stimuli and soluble gradients. Glioblastoma (U87, HGL21) and breast cancer (MDA-MB-231) cells in 1% agarose hydrogels were exposed to 50% compressive strain for 3 h (0.25-0.05 kPa). Live imaging showed that cells elongate and deflect vertically to the load. This stimulation is shown for the first time to differentially regulate metastasis-associated genes. Furthermore, a group of differentially expressed genes was identified in all cell types, both by microarrays and confirmed by RT-PCR for select genes (caveolin-1, integrin-β1, Rac1), indicating shared response mechanisms. These genes are functionally linked and involved in decreasing cell-cell contact, increasing ECM degradation, and ultimately promoting invasion. Caveolin could orchestrate these responses while the uPA and PI3K/Akt systems could play major roles. Future work will focus on specific molecular partnerships under compression and their impact on cancer progression.
Authors:
Zoe N Demou
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-18
Journal Detail:
Title:  Annals of biomedical engineering     Volume:  38     ISSN:  1521-6047     ISO Abbreviation:  Ann Biomed Eng     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-05     Completed Date:  2011-01-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0361512     Medline TA:  Ann Biomed Eng     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3509-20     Citation Subset:  IM    
Affiliation:
Northwestern University, Chicago, IL 60614-431, USA. zdemou@gmail.com
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / metabolism*,  pathology
Breast Neoplasms / metabolism*,  pathology
Cell Line, Tumor
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic*
Glioblastoma / metabolism*,  pathology
Humans
Models, Biological*
Neoplasm Metastasis
Neoplasm Proteins / biosynthesis*
Stress, Physiological*
Chemical
Reg. No./Substance:
0/Neoplasm Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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