Differential expression of metabolic genes in tumor and stromal components of primary and metastatic loci in pancreatic adenocarcinoma

Nina V. Chaika, Fang Yu, Vinee Purohit, Kamiya Mehla, Audrey J Lazenby, Dominick J DiMaio, Judy M. Anderson, Jen Jen Yeh, Keith R Johnson, Michael A Hollingsworth, Pankaj Singh

Research output: Contribution to journalArticle

46 Citations (Scopus)

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. Methods and Findings: 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.

Original languageEnglish (US)
Article numbere32996
JournalPloS one
Volume7
Issue number3
DOIs
StatePublished - Mar 7 2012

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adenocarcinoma
Tumors
Adenocarcinoma
Genes
Gene Expression
pancreatic neoplasms
loci
neoplasms
Gene expression
lesions (animal)
metastasis
Neoplasms
genes
Pancreatic Neoplasms
glycolysis
gene expression
Cells
Glycolysis
Pentoses
Neoplasm Metastasis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Differential expression of metabolic genes in tumor and stromal components of primary and metastatic loci in pancreatic adenocarcinoma. / Chaika, Nina V.; Yu, Fang; Purohit, Vinee; Mehla, Kamiya; Lazenby, Audrey J; DiMaio, Dominick J; Anderson, Judy M.; Yeh, Jen Jen; Johnson, Keith R; Hollingsworth, Michael A; Singh, Pankaj.

In: PloS one, Vol. 7, No. 3, e32996, 07.03.2012.

Research output: Contribution to journalArticle

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AU - DiMaio, Dominick J

AU - Anderson, Judy M.

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AU - Singh, Pankaj

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