Related Experiment Video
Updated: Jun 19, 2026
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Nodal as a biomarker for melanoma progression and a new therapeutic target for clinical intervention
Luigi Strizzi1, Lynne-Marie Postovit, Naira V Margaryan
1Children's Memorial Research Center, 2300 Children's Plaza, Box 222, Chicago, IL 60614, USA Tel.: +1 773 755 6327 lstrizzi@childrensmemorial.org.
Abstract:
Nodal, an embryonic morphogen belonging to the TGF-β superfamily, is an important regulator of embryonic stem cell fate. We have recently demonstrated that Nodal is expressed significantly in aggressive melanoma. Surprisingly, expression of the Nodal coreceptor, Cripto-1, was detected in only a small fraction of the melanoma tumor cell population, indicating a primary role for Cripto-1-independent signaling of Nodal in melanoma. In this review, we discuss how regulatory factors present in an embryonic environment, such as Lefty, can downregulate Nodal expression and inhibit tumorigenicity and plasticity of melanoma cells. Our translational studies show that antibodies against Nodal are capable of repressing melanoma vasculogenic mimicry and of inducing apoptosis in melanoma tumors in an in vivo lung-colonization assay. Our previous work and ongoing studies suggest that Nodal may represent a novel diagnostic marker and therapeutic target in melanoma.
Insights
Nodal signaling, crucial for embryonic development, is active in aggressive melanoma. Targeting Nodal with antibodies may offer a new therapeutic strategy for melanoma by inhibiting tumor growth and promoting cell death.
Area of Science:
- Developmental Biology
- Oncology
- Molecular Biology
Background:
- Nodal is a TGF-β superfamily member regulating embryonic stem cell fate.
- Nodal is significantly expressed in aggressive melanoma.
- Nodal coreceptor Cripto-1 is expressed in a small fraction of melanoma cells, suggesting Cripto-1-independent Nodal signaling.
Purpose of the Study:
- To review the role of Nodal signaling in melanoma.
- To discuss regulatory factors like Lefty in modulating Nodal expression and melanoma plasticity.
- To explore Nodal as a potential diagnostic marker and therapeutic target in melanoma.
Main Methods:
- Review of existing literature on Nodal and melanoma.
- Analysis of Nodal and Cripto-1 expression in melanoma.
- In vivo lung-colonization assay using antibodies against Nodal.
Main Results:
- Nodal is significantly expressed in aggressive melanoma.
- Lefty can downregulate Nodal expression, inhibiting melanoma tumorigenicity and plasticity.
- Antibodies against Nodal repressed melanoma vasculogenic mimicry and induced apoptosis in vivo.
Conclusions:
- Nodal signaling plays a significant role in melanoma progression.
- Nodal represents a potential diagnostic marker for melanoma.
- Targeting Nodal signaling may offer a novel therapeutic strategy for melanoma treatment.
