| Gene expression profiles in 3D tumor analogs indicate compressive strain differentially enhances metastatic potential. | |
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MedLine Citation:
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PMID: 20559731 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Zoe N Demou |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-18 |
Journal Detail:
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Title: Annals of biomedical engineering Volume: 38 ISSN: 1521-6047 ISO Abbreviation: Ann Biomed Eng Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-05 Completed Date: 2011-01-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0361512 Medline TA: Ann Biomed Eng Country: United States |
Other Details:
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Languages: eng Pagination: 3509-20 Citation Subset: IM |
Affiliation:
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Northwestern University, Chicago, IL 60614-431, USA. zdemou@gmail.com |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenocarcinoma
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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:
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0/Neoplasm Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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