Embryonic bone morphogenetic protein and nodal induce invasion in melanocytes and melanoma cells

Area of Science:

• Oncology
• Cell Biology
• Molecular Biology

Background:

• Advanced melanoma (stage IV) has limited survival despite current therapies.
• Therapeutic failure is linked to melanoma cell invasion and metastasis, driven by epithelial-mesenchymal transition (EMT).
• Bone morphogenetic protein (BMP) pathway inhibition previously abrogated EMT and melanoma cell migration.

Purpose of the Study:

• To investigate the role of BMP-2 in melanoma cell invasion and metastasis.
• To explore BMP-2, BMP-7, and nodal as inducers of EMT and invasion in melanoma.
• To evaluate the therapeutic potential of inhibiting BMP and nodal signaling pathways.

Main Methods:

• Quantified BMP-2 expression in melanoma cells and patient serum.
• Assessed melanoma cell invasion in chick and zebrafish embryos.
• Induced EMT and invasion using BMP agonists in melanoma cells and melanocytes.
• Blocked BMP or nodal signaling using antagonists and receptor inhibitors in skin reconstructs.

Main Results:

• BMP-2 is highly expressed in invasive melanoma cells and elevated in stage IV patient serum.
• BMP-2 promotes melanoma cell invasion in chick embryos.
• BMP-2, BMP-7, and nodal agonists induce EMT and invasion in melanoma cells and melanocytes.
• Inhibiting BMP or nodal signaling reduces melanoma cell EMT and invasion in skin models.

Conclusions:

• BMP-2 is a key driver of melanoma cell invasion and is upregulated in advanced disease.
• BMP and nodal signaling pathways promote melanoma EMT and invasiveness.
• Targeting EMT-inducing pathways, such as BMP signaling, represents a potential therapeutic strategy for advanced melanoma.