title: Investigation of cancer cell lines for peptide receptor-targeted drug development.
abstract: Many tumors highly express specific populations of G-protein-coupled receptors (GPCRs) that could be utilized for receptor-targeted therapy. We confirmed significant quantities of mRNAs specific for certain somatostatin (SST), vasoactive intestinal peptide (VIP), and bombesin (BN) receptors in various commercially available tumor cell lines. Very few of the tumor cell lines examined displayed the high receptor-binding affinity despite exhibiting the expression of appropriate mRNAs and proteins of the cognate receptors. However, binding assays establish that some tumor cell lines, such as pancreatic cancer CFPAC-1, prostate cancer DU-145, and pancreatic carcinoid BON, demonstrate high BN receptor binding. BON cells also demonstrate high somatostatin receptor (SSTR) affinity binding. We also found that tumor cell lines, such as BON and host cells expressing SST receptor subtypes 1 or 2 (CHO-R1 or CHO-R2), underwent a decrease in cell surface receptor density in multiple passages. BON and CHO-R2 cells also rapidly internalize a significant proportion of cell surface ligand-receptor complexes. The tumor cells CFPAC-1, DU-145, and BON with high receptor binding could be useful for peptide drug studies. BON cells were further applied to test SST/BN analogs and cytotoxic conjugates. Furthermore, the in vivo antitumor assay showed that the cytotoxic conjugate CPT-SST targeting all SSTR subtypes displayed a potent tumor-suppressive ability to BON tumors expressing multiple SSTR subtypes.
authors.affiliation: Department of Medicine, Peptide Research Laboratories, Tulane Health Sciences Center , New Orleans, LA 70112-2699, USA. lsun@tulane.edu
authors.forename: Lichun
authors.initials: L
authors.lastname: Sun
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.forename: L Vienna
authors.initials: LV
authors.lastname: Mackey
authors.forename: Lynsie M
authors.initials: LM
authors.lastname: Morris
authors.forename: Laura G
authors.initials: LG
authors.lastname: Franko-Tobin
authors.forename: Keith T
authors.initials: KT
authors.lastname: LePage
authors.forename: David H
authors.initials: DH
authors.lastname: Coy
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D015153:Blotting, Western; D001839:Bombesin / Q000031:analogs & derivatives / Q000737:chemistry; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D055808:Drug Discovery / Q000379:methods*; D008024:Ligands; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D011485:Protein Binding; D060888:Real-Time Polymerase Chain Reaction; D018004:Receptors, Bombesin / Q000096:biosynthesis / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000096:biosynthesis / Q000378:metabolism*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000096:biosynthesis / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008024:Ligands; D018004:Receptors, Bombesin; D017481:Receptors, Somatostatin; D018005:Receptors, Vasoactive Intestinal Peptide; D013004:Somatostatin; D001839:Bombesin