title: Cyclophilin A is overexpressed in human pancreatic cancer cells and stimulates cell proliferation through CD147.
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.
authors.affiliation: Molecular Surgeon Research Center, Houston, Texas, USA. minli@bcm.tmc.edu
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Qihui
authors.initials: Q
authors.lastname: Zhai
authors.forename: Uddalak
authors.initials: U
authors.lastname: Bharadwaj
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: William E
authors.initials: WE
authors.lastname: Fisher
authors.forename: Changyi
authors.initials: C
authors.lastname: Chen
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Yao
mesh_terms: D051926:Basigin / Q000276:immunology*; D001707:Biopsy, Needle; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D021983:Cyclophilins / Q000235:genetics* / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011336:Probability; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
chemical_list: D012334:RNA, Neoplasm; D051926:Basigin; D021983:Cyclophilins