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  • Title: Evidence of an intracellular angiotensin-generating system and non-AT1, non-AT2 binding site in a human pancreatic cell line.
    Author: Pérez-Díaz I, Guzmán C, Olivares-Reyes JA, Ramírez T, Gutierréz-Reyes G, Hiriart M, Robles-Díaz G.
    Journal: Pancreas; 2011 Jul; 40(5):701-7. PubMed ID: 21602736.
    Abstract:
    OBJECTIVES: 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.
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