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Background  Early metastasis and infiltration are survival limiting characteristics of pancreatic ductal adenocarcinoma (PDAC). Thus, PDAC is likely to harbor alterations in metastasis suppressor genes that may provide novel diagnostic and therapeutic opportunities. This study investigates a panel of metastasis suppressor genes in correlation to PDAC phenotype and examines promoter methylation for regulatory influence on metastasis suppressor gene expression and for its potential as a diagnostic tool.    Methods  Metastatic and invasive potential of 16 PDAC cell lines were quantified in an orthotopic mouse model and mRNA expression of 11 metastasis suppressor genes determined by quantitative RT-PCR. Analysis for promoter methylation was performed using methylation specific PCR and bisulfite sequencing PCR. Protein expression was determined by Western blot.    Results  In general, higher metastasis suppressor gene mRNA expression was not consistent with less aggressive phenotypes of PDAC. Instead, mRNA overexpression of several metastasis suppressor genes was found in PDAC cell lines vs. normal pancreatic RNA. Of the investigated metastasis suppressor genes, only higher  AKAP12  mRNA expression was correlated with decreased metastasis (P < 0.05) and invasion scores (P < 0.01) while higher  SERPINB5  mRNA expression was correlated with increased metastasis scores (P < 0.05). Both genes' promoters showed methylation, but only increased  SERPINB5  methylation was associated with loss of mRNA and protein expression (P < 0.05).  SERPINB5  methylation was also directly correlated to decreased metastasis scores (P < 0.05).    Conclusions   AKAP12  mRNA expression was correlated to attenuated invasive and metastatic potential and may be associated with less aggressive phenotypes of PDAC while no such evidence was obtained for the remaining metastasis suppressor genes. Increased  SERPINB5  mRNA expression was correlated to increased metastasis and mRNA expression was regulated by methylation. Thus,  SERPINB5  methylation was directly correlated to metastasis scores and may provide a diagnostic tool for PDAC.

SERPINB5 and AKAP12-- Expression and promoter methylation of metastasis suppressor genes in pancreatic ductal adenocarcinoma