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Updated: Jul 12, 2026

A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Embryonic and tumorigenic pathways converge via Nodal signaling: role in melanoma aggressiveness
Jolanta M Topczewska1, Lynne-Marie Postovit, Naira V Margaryan
1Program in Developmental Biology, Children's Memorial Research Center, Feinberg School of Medicine Northwestern University, 2300 Children's Plaza, Box 222, Chicago Illinois, 60614, USA.
Aggressive melanoma cells secrete Nodal, an embryonic morphogen, driving tumor progression and plasticity. Inhibiting Nodal signaling reduces melanoma invasiveness and promotes reversion to a normal cell phenotype, revealing a new therapeutic target.
Area of Science:
- Developmental Biology
- Cancer Biology
- Melanoma Research
Background:
- Bidirectional cellular communication is crucial for both cancer progression and embryonic development.
- Aggressive tumor cells exhibit phenotypic plasticity, mirroring properties of embryonic cells.
- The developing zebrafish serves as a biosensor for tumor-derived signals due to cellular similarities.
Purpose of the Study:
- To investigate the role of embryonic morphogens in melanoma pathogenesis.
- To identify novel molecular targets for regulating melanoma progression and plasticity.
Main Methods:
- Utilized zebrafish as a biosensor to detect tumor-derived signals.
- Analyzed Nodal presence in human metastatic melanoma and normal skin.
- Assessed the impact of Nodal signaling inhibition on melanoma cell behavior.
Main Results:
- Aggressive melanoma cells secrete Nodal, inducing ectopic embryonic axis formation.
- Nodal is present in metastatic tumors but not normal skin, suggesting its role in melanoma.
- Nodal inhibition decreased melanoma cell invasiveness, colony formation, and tumorigenicity.
- Inhibition of Nodal signaling promoted reversion of melanoma cells to a melanocytic phenotype.
Conclusions:
- Nodal signaling plays a critical role in melanoma cell plasticity and tumorigenicity.
- Nodal represents a previously unrecognized molecular target for melanoma therapy.
- Targeting Nodal signaling may offer a strategy to control melanoma progression and invasiveness.
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