Bi-Functional Peptides as a New Therapeutic Tool for Hepatocellular Carcinoma
Eric Savier,
Lorena Simon-Gracia,
Frederic Charlotte,
Pierre Tuffery,
Tambet Teesalu,
Olivier Scatton,
Angelita Rebollo
Affiliations
Eric Savier
Department of Hepatobiliary and Liver Transplantation Surgery, AP-HP, Pitié–Salpêtrière Hospital, Sorbonne Université, 75006 Paris, France
Lorena Simon-Gracia
Laboratory of Precision and Nanomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, 50090 Tartu, Estonia
Frederic Charlotte
Department of Pathology, AP-HP, Pitié–Salpêtrière Hospital, 75006 Paris, France
Pierre Tuffery
Biologie Fontionelle Adaptative (BFA), Unité Mixte de Recherche (UMR) 8251, Centre National de la Recherche Scientifique (CNRS) ERL U1133, Inserm, Université de Paris, 75006 Paris, France
Tambet Teesalu
Laboratory of Precision and Nanomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, 50090 Tartu, Estonia
Olivier Scatton
Department of Hepatobiliary and Liver Transplantation Surgery, AP-HP, Pitié–Salpêtrière Hospital, Sorbonne Université, 75006 Paris, France
Angelita Rebollo
Faculté de Pharmacie, Unité des Technologies Chimiques et Biologiques pour la Santé (UTCBS), Inserm U1267, Centre National de la Recherche Scientifique CNRS UMR8258, Université de Paris, 75006 Paris, France
Background: The interfering peptides that block protein–protein interactions have been receiving increasing attention as potential therapeutic tools. Methods: We measured the internalization and biological effect of four bi-functional tumor-penetrating and interfering peptides into primary hepatocytes isolated from three non-malignant and 11 hepatocellular carcinomas. Results: These peptides are internalized in malignant hepatocytes but not in non-malignant cells. Furthermore, the degree of peptide internalization correlated with receptor expression level and tumor aggressiveness levels. Importantly, penetration of the peptides iRGD-IP, LinTT1-IP, TT1-IP, and RPARPAR-IP induced apoptosis of the malignant hepatocytes without effect on non-malignant cells. Conclusion: Receptor expression levels correlated with the level of peptide internalization and aggressiveness of the tumor. This study highlights the potential to exploit the expression of tumor-penetrating peptide receptors as a predictive marker of liver tumor aggressiveness. These bi-functional peptides could be developed for personalized tumor treatment.
