title: Differential expression of metabolic genes in tumor and stromal components of primary and metastatic loci in pancreatic adenocarcinoma.
abstract: BACKGROUND
  Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States with a five-year survival rate of 6%. It is characterized by extremely aggressive tumor growth rate and high incidence of metastasis. One of the most common and profound biochemical phenotypes of animal and human cancer cells is their ability to metabolize glucose at high rates, even under aerobic conditions. However, the contribution of metabolic interrelationships between tumor cells and cells of the surrounding microenvironment to the progression of cancer is not well understood. We evaluated differential expression of metabolic genes and, hence, metabolic pathways in primary tumor and metastases of patients with pancreatic adenocarcinoma.
  
  
  RESULTS
  We analyzed the metabolic gene (those involved in glycolysis, tri-carboxylic acid pathway, pentose-phosphate pathway and fatty acid metabolism) expression profiles of primary and metastatic lesions from pancreatic cancer patients by gene expression arrays. We observed two principal results: genes that were upregulated in primary and most of the metastatic lesions; and genes that were upregulated only in specific metastatic lesions in a site-specific manner. Immunohistochemical (IHC) analyses of several metabolic gene products confirmed the gene expression patterns at the protein level. The IHC analyses also revealed differential tumor and stromal expression patterns of metabolic enzymes that were correlated with the metastasis sites.
  
  
  CONCLUSIONS
  Here, we present the first comprehensive studies that establish differential metabolic status of tumor and stromal components and elevation of aerobic glycolysis gene expression in pancreatic cancer.
authors.affiliation: The Eppley Institute for Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: Nina V
authors.initials: NV
authors.lastname: Chaika
authors.forename: Fang
authors.initials: F
authors.lastname: Yu
authors.forename: Vinee
authors.initials: V
authors.lastname: Purohit
authors.forename: Kamiya
authors.initials: K
authors.lastname: Mehla
authors.forename: Audrey J
authors.initials: AJ
authors.lastname: Lazenby
authors.forename: Dominick
authors.initials: D
authors.lastname: DiMaio
authors.forename: Judy M
authors.initials: JM
authors.lastname: Anderson
authors.forename: Jen Jen
authors.initials: JJ
authors.lastname: Yeh
authors.forename: Keith R
authors.initials: KR
authors.lastname: Johnson
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hollingsworth
authors.forename: Pankaj K
authors.initials: PK
authors.lastname: Singh
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism* / Q000556:secondary; D002952:Citric Acid Cycle / Q000235:genetics; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D010427:Pentose Phosphate Pathway / Q000235:genetics; D020543:Proteome; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D020543:Proteome; D012333:RNA, Messenger