Retrospective Proteomic Analysis of a Novel, Cancer Metastasis-Promoting RGD-Containing Peptide

Abstract Patients who undergo surgical extirpation of a primary liver carcinoma followed by radiotherapy and chemotherapy leading to complete remission are nevertheless known to develop cancerous metastases 3–10 years later. We retrospectively examined the blood sera collected over 8 years from 30 patients who developed bone metastases after the complete remission of liver cancer to identify serum proteins showing differential expression compared to patients without remission. We detected a novel RGD ( Arg-Gly-Asp)-containing peptide derived from the C-terminal portion of fibrinogen in the sera of metastatic patients that appeared to control the EMT ( epithelial-mesenchymal transition) of cancer cells, in a process associated with miR-199a-3p. The RGD peptideenhanced new blood vessel growth and increased vascular endothelial growth factor levels when introduced into fertilized chicken eggs. The purpose of this study was to enable early detection of metastatic cancer cells using the novel RGD peptideas a biomarker, and thereby develop new drugs for the treatment of metastatic cancer.