In vivo coherent Raman imaging of the melanomagenesis-associated pigment pheomelanin
Melanoma is the most deadly form of skin cancer with a yearly global incidence over 232,000 patients. Individuals with fair skin and red hair exhibit the highest risk for developing melanoma, with evidence suggesting the red/blond pigment known as pheomelanin may elevate melanoma risk through both U...
Main Authors: | , , , , , , , , |
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Format: | Article |
Language: | English |
Published: |
Nature Publishing Group,
2017-06-12T14:29:26Z.
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Online Access: | Get fulltext |
Summary: | Melanoma is the most deadly form of skin cancer with a yearly global incidence over 232,000 patients. Individuals with fair skin and red hair exhibit the highest risk for developing melanoma, with evidence suggesting the red/blond pigment known as pheomelanin may elevate melanoma risk through both UV radiation-dependent and -independent mechanisms. Although the ability to identify, characterize, and monitor pheomelanin within skin is vital for improving our understanding of the underlying biology of these lesions, no tools exist for real-time, in vivo detection of the pigment. Here we show that the distribution of pheomelanin in cells and tissues can be visually characterized non-destructively and noninvasively in vivo with coherent anti-Stokes Raman scattering (CARS) microscopy, a label-free vibrational imaging technique. We validated our CARS imaging strategy in vitro to in vivo with synthetic pheomelanin, isolated melanocytes, and the Mc1re/e, red-haired mouse model. Nests of pheomelanotic melanocytes were observed in the red-haired animals, but not in the genetically matched Mc1re/e; Tyrc/c ("albino-red-haired") mice. Importantly, samples from human amelanotic melanomas subjected to CARS imaging exhibited strong pheomelanotic signals. This is the first time, to our knowledge, that pheomelanin has been visualized and spatially localized in melanocytes, skin, and human amelanotic melanomas. BRIDGE (Project) (Grant 222700) Canadian Institutes of Health Research Frances Keany Rickard Fund Fellowship National Institutes of Health (U.S.) (5P01 CA163222-03) National Institutes of Health (U.S.) (5R01 AR043369-19) Dr. Miriam and Sheldon G. Adelson Medical Research Foundation |
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