DigitalCommons@UNMC

Title

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

Authors

Nina V. Chaika, University of Nebraska Medical CenterFollow
Fang Yu, University of Nebraska Medical CenterFollow
Vinee Purohit, University of Nebraska Medical Center
Kamiya Mehla, University of Nebraska Medical CenterFollow
Audrey J. Lazenby, University of Nebraska Medical CenterFollow
Dominick J. DiMaio, University of Nebraska Medical CenterFollow
Judy M. Anderson, University of Nebraska Medical Center
Jen Jen Yeh, University of North Carolina at Chapel Hill
Keith R. Johnson, Univerity of Nebraska Medical CenterFollow
Michael A. Hollingsworth, University of Nebraska Medical CenterFollow
Pankaj K. Singh, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

PLoS One

Publication Date

2012

Volume

7

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.

MeSH Headings

Adenocarcinoma, Citric Acid Cycle, Cluster Analysis, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Glycolysis, Humans, Metabolic Networks and Pathways, Pancreatic Neoplasms, Pentose Phosphate Pathway, Proteome, RNA, Messenger, Stromal Cells

DOI Link

10.1371/journal.pone.0032996

ISSN

1932-6203

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

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.; and Singh, Pankaj K., "Differential expression of metabolic genes in tumor and stromal components of primary and metastatic loci in pancreatic adenocarcinoma." (2012). Journal Articles: Eppley Institute. 27.
https://digitalcommons.unmc.edu/eppley_articles/27