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Biol Open. 2018 Jan 11;7(1). pii: bio030817. doi: 10.1242/bio.030817.

NGF reprograms metastatic melanoma to a bipotent glial-melanocyte neural crest-like precursor.

Author information

1
Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
2
Duke University, Margolis Center for Health Policy, Washington, DC 20004, USA.
3
Department of Biology, Brigham Young University-Idaho, Rexburg, ID 83460, USA.
4
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
5
Stowers Institute for Medical Research, Kansas City, MO 64110, USA pmk@stowers.org.
6
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.

Abstract

Melanoma pathogenesis from normal neural crest-derived melanocytes is often fatal due to aggressive cell invasion throughout the body. The identification of signals that reprogram de-differentiated, metastatic melanoma cells to a less aggressive and stable phenotype would provide a novel strategy to limit disease progression. In this study, we identify and test the function of developmental signals within the chick embryonic neural crest microenvironment to reprogram and sustain the transition of human metastatic melanoma to a neural crest cell-like phenotype. Results reveal that co-culture of the highly aggressive and metastatic human melanoma cell line C8161 upregulate a marker of melanosome formation (Mart-1) in the presence of embryonic day 3.5 chick trunk dorsal root ganglia. We identify nerve growth factor (NGF) as the signal within this tissue driving Mart-1 re-expression and show that NGF receptors trkA and p75 cooperate to induce Mart-1 re-expression. Furthermore, Mart-1 expressing C8161 cells acquire a gene signature of poorly aggressive C81-61 cells. These data suggest that targeting NGF signaling may yield a novel strategy to reprogram metastatic melanoma toward a benign cell type.

KEYWORDS:

Chick embryonic microenvironment; Human; Melanoma; Metastasis; Nerve growth factor; Neural crest

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