Limits...
Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis.

Sugihara K, Kobayashi Y, Suzuki A, Tamura N, Motamedchaboki K, Huang CT, Akama TO, Pecotte J, Frost P, Bauer C, Jimenez JB, Nakayama J, Aoki D, Fukuda MN - Nat Commun (2014)

Bottom Line: Endometriosis is a common gynaecological disease associated with pelvic pain and infertility.Here we identify an endometriosis-targeting peptide that is internalized by cells, designated z13, using phage display.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.

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.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemistry of paraffin tissue sections using mouse monoclonal anti-CNGB3 antibody.(a) Endometriosis lesions from an endometriosis patient. Scale bar, 500 μm. (b) An endometrial gland in endometriosis tissue. Scale bar, 200 μm. (c) Peritoneal tissue from a cycling woman without endometriosis. Scale bar, 100 μm. (d) Peritoneal tissue from an endometriosis patient. Scale bar, 100 μm. (e) Uterine endometrium at secretory phase. Scale bar, 200 μm. (f) Uterine endometrium at proliferative phase. Scale bar, 200 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4109024&req=5

f3: Immunohistochemistry of paraffin tissue sections using mouse monoclonal anti-CNGB3 antibody.(a) Endometriosis lesions from an endometriosis patient. Scale bar, 500 μm. (b) An endometrial gland in endometriosis tissue. Scale bar, 200 μm. (c) Peritoneal tissue from a cycling woman without endometriosis. Scale bar, 100 μm. (d) Peritoneal tissue from an endometriosis patient. Scale bar, 100 μm. (e) Uterine endometrium at secretory phase. Scale bar, 200 μm. (f) Uterine endometrium at proliferative phase. Scale bar, 200 μm.

Mentions: To examine CNGB3 protein expression in endometriosis, we generated a mouse monoclonal antibody against a peptide sequence of human CNGB3, corresponding to K721 to P750 within the cytoplasmic domain (Supplementary Fig. 4). Antibody specificity was validated by immunostaining of CNGB3–MYC expressed in HeLa cells (Supplementary Fig. 6). This antibody robustly stained glandular epithelia of endometriosis in tissue sections (Fig. 3a,b). When we evaluated endometriosis tissue sections from 35 endometriosis patients, we found that 31 specimens showed strongly positive immunostaining and 4 showed weak/negative immunostaining. Peritoneal surfaces from cycling women without endometriosis were not stained by this antibody, whereas those from endometriosis patients were stained by this antibody (Fig. 3c,d), suggesting that endometrial cells are spread across a wide area on the peritoneum of endometriosis patients. Eutopic endometrial tissues at secretory and proliferative phases were weakly stained by this antibody (Fig. 3e,f). Immunohistochemistry of human tissues showed that this antibody did not stain the surface of organs facing the peritoneal cavity (data not shown).


Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis.

Sugihara K, Kobayashi Y, Suzuki A, Tamura N, Motamedchaboki K, Huang CT, Akama TO, Pecotte J, Frost P, Bauer C, Jimenez JB, Nakayama J, Aoki D, Fukuda MN - Nat Commun (2014)

Immunohistochemistry of paraffin tissue sections using mouse monoclonal anti-CNGB3 antibody.(a) Endometriosis lesions from an endometriosis patient. Scale bar, 500 μm. (b) An endometrial gland in endometriosis tissue. Scale bar, 200 μm. (c) Peritoneal tissue from a cycling woman without endometriosis. Scale bar, 100 μm. (d) Peritoneal tissue from an endometriosis patient. Scale bar, 100 μm. (e) Uterine endometrium at secretory phase. Scale bar, 200 μm. (f) Uterine endometrium at proliferative phase. Scale bar, 200 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109024&req=5

f3: Immunohistochemistry of paraffin tissue sections using mouse monoclonal anti-CNGB3 antibody.(a) Endometriosis lesions from an endometriosis patient. Scale bar, 500 μm. (b) An endometrial gland in endometriosis tissue. Scale bar, 200 μm. (c) Peritoneal tissue from a cycling woman without endometriosis. Scale bar, 100 μm. (d) Peritoneal tissue from an endometriosis patient. Scale bar, 100 μm. (e) Uterine endometrium at secretory phase. Scale bar, 200 μm. (f) Uterine endometrium at proliferative phase. Scale bar, 200 μm.
Mentions: To examine CNGB3 protein expression in endometriosis, we generated a mouse monoclonal antibody against a peptide sequence of human CNGB3, corresponding to K721 to P750 within the cytoplasmic domain (Supplementary Fig. 4). Antibody specificity was validated by immunostaining of CNGB3–MYC expressed in HeLa cells (Supplementary Fig. 6). This antibody robustly stained glandular epithelia of endometriosis in tissue sections (Fig. 3a,b). When we evaluated endometriosis tissue sections from 35 endometriosis patients, we found that 31 specimens showed strongly positive immunostaining and 4 showed weak/negative immunostaining. Peritoneal surfaces from cycling women without endometriosis were not stained by this antibody, whereas those from endometriosis patients were stained by this antibody (Fig. 3c,d), suggesting that endometrial cells are spread across a wide area on the peritoneum of endometriosis patients. Eutopic endometrial tissues at secretory and proliferative phases were weakly stained by this antibody (Fig. 3e,f). Immunohistochemistry of human tissues showed that this antibody did not stain the surface of organs facing the peritoneal cavity (data not shown).

Bottom Line: Endometriosis is a common gynaecological disease associated with pelvic pain and infertility.Here we identify an endometriosis-targeting peptide that is internalized by cells, designated z13, using phage display.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.

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.

No MeSH data available.


Related in: MedlinePlus