Soluble melanoma cell adhesion molecule (sMCAM/sCD146) promotes angiogenic effects on endothelial progenitor cells...

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• The circulating variant of melanoma cell adhesion molecule (sCD146) is implicated in inflammation and angiogenesis, but its intracellular signaling remains unclear.
• sCD146 levels vary in different diseases, highlighting its pathological relevance.
• Understanding sCD146's molecular interactions is crucial for developing targeted therapies.

Purpose of the Study:

• To identify proteins that interact with sCD146 within endothelial progenitor cells (EPCs).
• To elucidate the intracellular signaling pathways activated by sCD146-angiomotin interaction.
• To investigate the role of angiomotin in mediating the proangiogenic effects of sCD146.

Main Methods:

• Peptide pulldown and mass spectrometry were used to identify sCD146-binding proteins.
• Enzyme-linked immunosorbent assay (ELISA), homogeneous time-resolved fluorescence, and cell-based binding assays confirmed protein interactions.
• Angiomotin silencing and inhibition were employed to assess its role in sCD146 signaling.

Main Results:

• Angiomotin was identified as an sCD146-associated protein in EPCs.
• sCD146 binding to angiomotin activated multiple intracellular transduction pathways.
• Silencing or inhibiting angiomotin abrogated sCD146-induced EPC migration, proliferation, and capillary-like structure formation.
• Inhibition of sCD146 effects by angiostatin and recombinant angiomotin further supported the interaction.

Conclusions:

• A novel signaling pathway is described where sCD146 binds to angiomotin, triggering proangiogenic responses.
• This interaction activates key transduction pathways, mediating the angiogenic effects of sCD146.
• The findings identify new target cells for sCD146 and offer potential therapeutic strategies for ischemic diseases using EPCs.