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Updated: Feb 18, 2026
Direct Reprogramming of Mouse Fibroblasts into Melanocytes
Published on: August 27, 2021
NGF reprograms metastatic melanoma to a bipotent glial-melanocyte neural crest-like precursor
Jennifer C Kasemeier-Kulesa1, Morgan H Romine2, Jason A Morrison1
1Stowers Institute for Medical Research, Kansas City, MO 64110, 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.
Insights
Researchers discovered that nerve growth factor (NGF) can reprogram aggressive melanoma cells. This developmental signal encourages melanoma cells to revert to a less aggressive, neural crest-like state, offering a potential new treatment strategy.
Area of Science:
- Developmental Biology
- Cancer Biology
- Cellular Reprogramming
Background:
- Melanoma, derived from neural crest melanocytes, is often fatal due to its aggressive metastatic potential.
- Reprogramming metastatic melanoma cells to a less aggressive phenotype is a key therapeutic goal.
Purpose of the Study:
- To identify developmental signals that can reprogram metastatic melanoma cells to a neural crest cell-like phenotype.
- To investigate the potential of these signals to limit melanoma disease progression.
Main Methods:
- Co-culture of human metastatic melanoma cells (C8161) with embryonic chick dorsal root ganglia.
- Identification of signaling molecules and receptors involved in cellular reprogramming.
- Analysis of gene expression signatures to assess changes in melanoma cell aggressiveness.
Main Results:
- Co-culture induced upregulation of Mart-1, a melanosome formation marker, in C8161 melanoma cells.
- Nerve growth factor (NGF) was identified as the key signal driving Mart-1 re-expression.
- NGF receptors (trkA and p75) were shown to cooperate in inducing Mart-1 re-expression.
- Mart-1 expressing melanoma cells exhibited a gene signature associated with reduced aggressiveness.
Conclusions:
- Nerve growth factor (NGF) signaling can reprogram metastatic melanoma cells towards a less aggressive, neural crest-like phenotype.
- Targeting NGF signaling represents a novel therapeutic strategy for treating metastatic melanoma.
