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Modulation of matrix elasticity with PEG hydrogels to study melanoma drug responsiveness

Paper ID Volume ID Publish Year Pages File Format Full-Text
5928 448 2014 9 PDF Available
Title
Modulation of matrix elasticity with PEG hydrogels to study melanoma drug responsiveness
Abstract

Metastatic melanoma is highly resistant to drug treatment, and the underlying mechanisms of this resistance remain unclear. Increased tissue stiffness is correlated with tumor progression, but whether increased tissue stiffness contributes to treatment resistance in melanoma is not known. To investigate the effect of substrate stiffness on melanoma cell treatment responsiveness, PEG hydrogels were utilized as a cell culture system to precisely vary matrix elasticity and investigate melanoma cell responses to a commercially available pharmacological inhibitor (PLX4032). The tensile moduli were varied between 0.6 and 13.1 kPa (E) and the effects of PLX4032 on metabolic activity, apoptosis, and proliferation were evaluated on human cell lines derived from radial growth phase (WM35) and metastatic melanoma (A375). The A375 cells were found to be stiffness-independent; matrix elasticity did not alter cell morphology or apoptosis with PLX4032 treatment. The WM35 cells, however, were more dependent on substrate modulus, displaying increased apoptosis and smaller focal adhesions on compliant substrates. Culturing melanoma cells on PEG hydrogels revealed stage-dependent responses to PLX4032 that would have otherwise been masked if cultured strictly on TCPS. These findings demonstrate the utility of PEG hydrogels as a versatile in vitro culture platform with which to investigate the molecular mechanisms of melanoma biology and treatment responsiveness.

Keywords
BRAF; Cell viability; ECM (extracellular matrix); Elasticity; Hydrogel; Photopolymerization
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Modulation of matrix elasticity with PEG hydrogels to study melanoma drug responsiveness
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 35, Issue 14, May 2014, Pages 4310–4318
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us