Detecting human melanoma cell re-differentiation following BRAF or heat shock protein 90 inhibition using photoacoustic and magnetic resonance imaging.
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Date
2017-08-15ICR Author
Author
Shah, A
Delgado-Goni, T
Casals Galobart, T
Wantuch, S
Jamin, Y
Leach, MO
Robinson, SP
Bamber, J
Beloueche-Babari, M
Type
Journal Article
Metadata
Show full item recordAbstract
Targeted therapies specific to the BRAF-MEK-ERK signaling pathway have shown great promise in the treatment of malignant melanoma in the last few years, with these drugs now commonly used in clinic. Melanoma cells treated using these agents are known to exhibit increased levels of melanin pigment and tyrosinase activity. In this study we assessed the potential of non-invasive imaging approaches (photoacoustic imaging (PAI) and magnetic resonance imaging (MRI)) to detect melanin induction in SKMEL28 human melanoma cells, following inhibition of Hsp90 and BRAF signaling using 17-AAG and vemurafenib, respectively. We confirmed, using western blot and spectrophotometry, that Hsp90 or BRAF inhibitor-induced melanoma cell differentiation resulted in an upregulation of tyrosinase and melanin expression levels, in comparison to control cells. This post-treatment increase in cellular pigmentation induced a significant increase in PAI signals that are spectrally identifiable and shortening of the MRI relaxation times T 1 and [Formula: see text]. This proof-of-concept study demonstrates the potential of MRI and PAI for detecting the downstream cellular changes induced by Hsp90 and BRAF-MEK-targeted therapies in melanoma cells with potential significance for in vivo imaging.
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Subject
Cell Line, Tumor
Humans
Melanoma
Proto-Oncogene Proteins B-raf
Antineoplastic Agents
Protein Kinase Inhibitors
Magnetic Resonance Imaging
Cell Differentiation
Cell Proliferation
Pigments, Biological
HSP90 Heat-Shock Proteins
Photoacoustic Techniques
Research team
Magnetic Resonance
Pre-Clinical MRI
Ultrasound & Optical Imaging
Language
eng
Date accepted
2017-07-04
License start date
2017-08-15
Citation
Scientific reports, 2017, 7 (1), pp. 8215 - ?
Publisher
NATURE PUBLISHING GROUP