title: Effects of somatostatin and octreotide on the interactions between neoplastic gastroenteropancreatic endocrine cells and endothelial cells: a comparison between in vitro and in vivo properties.
abstract: OBJECTIVE
  Experimental studies in vitro suggest that somatostatin and some of its analogues used in clinical practice, such as octreotide, may have potent antiangiogenic properties. However, the clinical transposition of these data is difficult.
  
  
  METHODS
  To address this issue, we designed a comparative study of the effects of somatostatin and octreotide on the interactions between neoplastic endocrine cells and endothelial cells in several in vitro and in vivo experimental models, including primary cultures of human umbilical vein endothelial cells (HUVEC), indirect cocultures between HUVEC and the somatostatin-producing endocrine cell line STC-1, and an animal model of intrahepatic dissemination of STC-1 cells.
  
  
  RESULTS
  10(-8)M octreotide markedly inhibited both basal and VEGF-stimulated HUVEC proliferation, had no effect on endothelial cell migration, but inhibited endothelial tubule formation. HUVEC cocultured with the somatostatin- and VEGF-producing STC-1 cells presented a markedly decreased proliferation, a slightly increased motility and an increased capacity of tubule formation; in this system, the inhibition of endothelial cell proliferation was abolished by neutralizing anti-somatostatin but was restored in the presence of anti-VEGF antibodies. This suggests that somatostatin is able to antagonize the effects of VEGF on endothelial cell proliferation but not on endothelial cell sprouting. Finally, no significant effect of octreotide on tumor growth and intratumoral microvascular density was detected in an experimental model of intrahepatic dissemination of STC-1 cells.
  
  
  CONCLUSIONS
  The in vitro antiangiogenic effects of somatostatin and its analogues are likely to be efficiently counterbalanced in the tumor microenvironment by the concomitant release of proangiogenic factors like VEGF.
authors.affiliation: Lyon Cancer Research Center, Team 4, INSERM UMR1052/CNRS UMR5286, Lyon, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Walter
authors.forename: Juliette
authors.initials: J
authors.lastname: Hommell-Fontaine
authors.forename: Géraldine
authors.initials: G
authors.lastname: Gouysse
authors.forename: Céline
authors.initials: C
authors.lastname: Pourreyron
authors.forename: Mimoun
authors.initials: M
authors.lastname: Nejjari
authors.forename: Karine
authors.initials: K
authors.lastname: Villaume
authors.forename: Sylvain
authors.initials: S
authors.lastname: Causeret
authors.forename: Valérie
authors.initials: V
authors.lastname: Hervieu
authors.forename: Gilles
authors.initials: G
authors.lastname: Poncet
authors.forename: Colette
authors.initials: C
authors.lastname: Roche
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Scoazec
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002277:Carcinoma / Q000473:pathology; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D019858:Enteroendocrine Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D015282:Octreotide / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000473:pathology; D013004:Somatostatin / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D013004:Somatostatin; D015282:Octreotide