title: Somatostatin and somatostatin analogues reduce PDGF-induced endometrial cell proliferation and motility.
abstract: BACKGROUND
  Endometriosis is characterized by ectopic implantation of endometrial cells, which show increased proliferation and migration. Somatostatin (SST) and its analogues inhibit normal and cancer cell growth and motility through the SST receptors, sst1-5. Cortistatin (CST), which displays high structural and functional homology with SST, binds all ssts, as well as MrgX2. Our objective was to investigate the gene expression of the SST/CST system and to determine the effect of SST and its analogues on platelet-derived growth factor (PDGF)-induced proliferation and motility in telomerase-immortalized human endometrial stromal cell (T HESC) line and in primary endometrial stromal cell (ESCs) isolated from human endometriotic tissues.
  
  
  METHODS
  Ectopic endometrial tissues were collected from women (n= 23) undergoing laparoscopic surgery for endometriosis (Stage III/IV). Gene expression was evaluated by real-time PCR, cell motility by wound healing assay, protein expression and β-actin rearrangement by immunofluorescence, cell proliferation by the Alamar blue assay and ERK1/2 and Akt phosphorylation by western blot.
  
  
  RESULTS
  Human endometriotic tissues, primary ESCs and T HESCs expressed SST, CST and ssts. SST, its analogues SOM230 and octreotide, as well as CST, counteracted PDGF-induced proliferation and migration in both ESCs and T HESCs. SST also inhibited vascular endothelial growth factor and metalloprotease-2 mRNA expression, and reduced basal and PDGF-induced ERK1/2 phosphorylation.
  
  
  CONCLUSIONS
  These results indicate that the SST/CST system is expressed in endometriotic tissues and cells. The inhibitory effects of SST and its analogues on PDGF-induced proliferation and motility suggest that these peptides may represent promising tools in the treatment of endometriosis.
authors.affiliation: Laboratory of Molecular and Cellular Endocrinology, Department of Internal Medicine, University of Turin, Corso Dogliotti 14, 10126 Turin, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Annunziata
authors.forename: Raul M
authors.initials: RM
authors.lastname: Luque
authors.forename: Mario
authors.initials: M
authors.lastname: Durán-Prado
authors.forename: Alessandra
authors.initials: A
authors.lastname: Baragli
authors.forename: Cristina
authors.initials: C
authors.lastname: Grande
authors.forename: Marco
authors.initials: M
authors.lastname: Volante
authors.forename: Manuel D
authors.initials: MD
authors.lastname: Gahete
authors.forename: Francesco
authors.initials: F
authors.lastname: Deltetto
authors.forename: Marco
authors.initials: M
authors.lastname: Camanni
authors.forename: Ezio
authors.initials: E
authors.lastname: Ghigo
authors.forename: Justo P
authors.initials: JP
authors.lastname: Castaño
authors.forename: Riccarda
authors.initials: R
authors.lastname: Granata
mesh_terms: D002465:Cell Movement; D049109:Cell Proliferation; D004715:Endometriosis / Q000378:metabolism; D004717:Endometrium / Q000166:cytology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology; D017154:Stromal Cells / Q000166:cytology; D014945:Wound Healing
chemical_list: C480039:MRGPRX2 protein, human; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D010982:Platelet-Derived Growth Factor; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; C099323:cortistatin; D013004:Somatostatin