title: Evidence of an intracellular angiotensin-generating system and non-AT1, non-AT2 binding site in a human pancreatic cell line.
abstract: OBJECTIVE
  To assess the presence of a local angiotensin-generating systems (LAGS) and its participation in tumor growth in the human pancreatic cancer derived cell line Capan-1.
  
  
  METHODS
  Capan-1 cells were cultured in Dulbecco modified Eagle medium, and angiotensin I was assayed by radioimmunoassay and angiotensin II and vascular endothelial growth factor were assayed by enzyme-linked immunosorbent assay in the supernatant. Immunohistochemistry and reverse transcription-polymerase chain reaction were performed for the expression of AT1 and AT2 receptors. Angiotensin II binding assays and blockade were studied.
  
  
  RESULTS
  High levels of both angiotensins I and II were found in Capan-1 cells, although neither angiotensin I nor angiotensin II was detected in the cell culture supernatant. Reverse transcription-polymerase chain reaction and immunocytochemistry revealed that Capan-1 cells do not express AT1 and AT2 receptors; however, specific binding to the cell membrane was identified for angiotensin II. Neither exogenous angiotensin II nor Dup753 (specific AT1 receptor blocker) affected Capan-1 cells' proliferation or vascular endothelial growth factor secretion.
  
  
  CONCLUSIONS
  Detection of both angiotensin I and angiotensin II along with specific binding of angiotensin II in Capan-1 cells provides evidence of the existence of a LAGS that operates in an intracrine manner. Intracellular angiotensin II may play a role in the aggressiveness of pancreatic cancer and is a possible target for therapeutic agents.
authors: Laboratorio de Hígado, Páncreas y Motilidad, Unidad de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México/Hospital General de México, Mexico.
authors: Iván
authors: I
authors: Pérez-Díaz
authors: Carolina
authors: C
authors: Guzmán
authors: Jesús Alberto
authors: JA
authors: Olivares-Reyes
authors: Teresa
authors: T
authors: Ramírez
authors: Gabriela
authors: G
authors: Gutierréz-Reyes
authors: Marcia
authors: M
authors: Hiriart
authors: Guillermo
authors: G
authors: Robles-Díaz