title: Targeting of hepatocellular carcinoma with glypican-3-targeting peptide ligand.
abstract: Hepatocellular carcinoma is a common malignancy. The carcinoma cells express glypican-3 (GPC-3) on the cell membrane. GPC-3 is also expressed in melanoma cells. Therefore, GPC-3 might be a potential target for tumor imaging or therapy. Here, proteomic mass spectrometry was used to identify peptides that target GPC-3-expressing tumors. A mammalian expression vector expressing a FLAG-GPC-3 fusion protein was cloned for immunoprecipitation. With the use of liposomes, the vector was transfected into HepG2 (HepG2/FLAG-GPC-3) and HEK 293 cells, and the transfected cell lines were selected with geneticin. HepG2/FLAG-GPC-3 cells were used for immunoprecipitation of FLAG-GPC-3 fusion protein. Seven peptide candidates (L1-L7) were selected for GPC-3-targeting ligands by mass spectrometric analysis. The L5 peptide with 14 amino acids (Arg-Leu-Asn-Val-Gly-Gly-Thr-Tyr-Phe-Leu-Thr-Thr-Arg-Gln) showed selective binding to the GPC-3-expressing tumor cells, as did a shortened L5 peptide (L5-2) with seven amino acids (Tyr-Phe-Leu-Thr-Thr-Arg-Gln). These peptide ligands have potential as targeting moieties to GPC-3-expressing tumors for diagnostic and/or therapeutic purposes.
authors: Department of Nuclear Medicine, Kyungpook National University School of Medicine, Chung Gu, Daegu, South Korea.
authors: You La
authors: YL
authors: Lee
authors: Byeong-Cheol
authors: BC
authors: Ahn
authors: Yongjin
authors: Y
authors: Lee
authors: Sang-Woo
authors: SW
authors: Lee
authors: Je-Yoel
authors: JY
authors: Cho
authors: Jaetae
authors: J
authors: Lee
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D017931:DNA Primers; D016503:Drug Delivery Systems; D016650:Fluorescein-5-isothiocyanate; D053673:Glypicans / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008024:Ligands; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D017931:DNA Primers; C105937:GPC3 protein, human; D053673:Glypicans; D008024:Ligands; D010455:Peptides; D012333:RNA, Messenger; D016650:Fluorescein-5-isothiocyanate