Cyclophilin A is overexpressed in human pancreatic cancer cells and stimulates cell proliferation through CD147

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Abstract
BACKGROUND Although overexpression of cyclophilin A (CypA) is associated with several types of cancer, its role in pancreatic cancer has not been studied. In this study the expression of CypA and its receptor CD147 on pancreatic cancer was determined as well as the effect of exogenous CypA on pancreatic cancer cell proliferation. METHODS The expression of CypA and CD147 in human pancreatic cancer cell lines and tissues was determined with real‐time reverse transcriptase polymerase chain reaction (RT‐PCR), Western blot, and immunostaining. Cell proliferation in response to CypA was performed by [3H]thymidine incorporation assay. Phosphorylation of MAPK and cytokine secretion profiles in pancreatic cancer cells were determined by using the Bio‐Plex phosphoprotein assay and cytokine assay. RESULTS Pancreatic cancer cell lines expressed significantly higher levels of CypA and CD147 than normal human pancreatic ductal epithelium (HPDE) cells. Expression of CypA and CD147 was also substantially higher in human pancreatic adenocarcinoma tissues than those in normal pancreatic tissues. Addition of exogenous CypA significantly stimulated pancreatic cancer cell proliferation in a dose‐dependent manner and this effect was effectively blocked by pretreatment with anti‐CD147 antibody. In addition, CypA activated ERK1/2 and p38 MAPK signaling pathways and increased the secretion of 2 key cytokines IL‐5 and IL‐17 in Panc‐1 cells. CONCLUSIONS The expression of CypA and CD147 was significantly increased in both pancreatic cancer cell lines and tissues. Exogenous CypA promotes pancreatic cancer cell growth, which may be mediated through the interaction with CD147 and the activation of ERK1/2 and p38 MAPKs. Cancer 2006. © 2006 American Cancer Society.