title: Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis.
abstract: Endometriosis is a common gynaecological disease associated with pelvic pain and infertility. Current treatments include oral contraceptives combined with nonsteroidal anti-inflammatory drugs or surgery to remove lesions, all of which provide a temporary but not complete cure. Here we identify an endometriosis-targeting peptide that is internalized by cells, designated z13, using phage display. As most endometriosis occurs on organ surfaces facing the peritoneum, we subtracted a phage display library with female mouse peritoneum tissue and selected phage clones by binding to human endometrial epithelial cells. Proteomics analysis revealed the z13 receptor as the cyclic nucleotide-gated channel β3, a sorting pathway protein. We then linked z13 with an apoptosis-inducing peptide and with an endosome-escaping peptide. When these peptides were co-administered into the peritoneum of baboons with endometriosis, cells in lesions selectively underwent apoptosis with no effect on neighbouring organs. Thus, this study presents a strategy that could be useful to treat peritoneal endometriosis in humans.
authors.affiliation: Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sugihara
authors.affiliation: Tumor Microenvironment, Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Shinanomachi 35, Tokyo 160-8582, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Tumor Microenvironment, Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: N
authors.initials: N
authors.lastname: Tamura
authors.affiliation: Tumor Microenvironment, Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: K
authors.initials: K
authors.lastname: Motamedchaboki
authors.affiliation: Tumor Microenvironment, Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: C-T
authors.initials: CT
authors.lastname: Huang
authors.affiliation: Tumor Microenvironment, Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: T O
authors.initials: TO
authors.lastname: Akama
authors.affiliation: Southwest National Primate Research Center, Texas Biomedical Research Institute, 7620 NW Loop 410, San Antonio, Texas 78245, USA.
authors.forename: J
authors.initials: J
authors.lastname: Pecotte
authors.affiliation: Southwest National Primate Research Center, Texas Biomedical Research Institute, 7620 NW Loop 410, San Antonio, Texas 78245, USA.
authors.forename: P
authors.initials: P
authors.lastname: Frost
authors.affiliation: Southwest National Primate Research Center, Texas Biomedical Research Institute, 7620 NW Loop 410, San Antonio, Texas 78245, USA.
authors.forename: C
authors.initials: C
authors.lastname: Bauer
authors.affiliation: Southwest National Primate Research Center, Texas Biomedical Research Institute, 7620 NW Loop 410, San Antonio, Texas 78245, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Jimenez
authors.affiliation: Department of Molecular Pathology, Shinshu University Graduate School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Nakayama
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Shinanomachi 35, Tokyo 160-8582, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Aoki
authors.affiliation: Tumor Microenvironment, Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: M N
authors.initials: MN
authors.lastname: Fukuda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004715:Endometriosis / Q000188:drug therapy* / Q000473:pathology; D004717:Endometrium / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy / Q000379:methods*; D010215:Papio; D019151:Peptide Library; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D010532:Peritoneal Diseases / Q000188:drug therapy / Q000473:pathology
chemical_list: C415904:CNGB3 protein, human; D054815:Cyclic Nucleotide-Gated Cation Channels; D004268:DNA-Binding Proteins; D019151:Peptide Library; D010455:Peptides; C095988:ZNF473 protein, human