Inhibition of Bone Morphogenetic Proteins Signaling Suppresses Metastasis Melanoma: a Proteomics Approach

Background: Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β superfamily, known to promote the tumor invasion and metastasis. There are continual progresses in understanding the role of BMP signaling pathways in carcinogenesis. However, the biological significance of BMPs in human melanoma has received very little attention. The study aimed to explore the effect of BMP inhibition on melanoma treated with LDN193189 (BMP inhibitor) using a quantitative proteomics approach in a melanoma xenograft model.

Materials And Methods: Melanoma tumor was induced in C57BL6 mice and treated intraperitoneally with LDN193189 for ten consecutive days. Post-treatment, tumors were collected, and comparative proteomics was performed using a high-resolution Orbitrap Fusion Tribrid mass spectrometer.

Results: Treatment of melanoma with LDN193189 at 3 mg/kg body weight twice daily showed a significant decrease in the growth rate of the tumor compared to the other doses tested. Quantitative proteomic profiling identified 3231 proteins. Bioinformatics analysis of the 131 differentially expressed proteins selected by their relative abundance revealed that LDN193189 induces alterations in the cellular and metabolic process and the proteins that are involved in protein binding and catalytic activity in melanoma.

Conclusions: Down-regulation of metallothionein (MT) 1 and MT2, emerging proteins for their role in tumor formation, progression, and drug resistance and transcription factor EB that plays a crucial role in the regulation of basic cellular processes, such as lysosomal biogenesis and autophagy, were identified upon inhibition of the BMP pathway in melanoma, suggesting their roles in melanoma growth. Understanding the role of these proteins will provide new directions for treating cancer.