[Frontiers in Bioscience 17, 1761-1774, January 1, 2012]

Hyperglycemia as a mechanism of pancreatic cancer metastasis

Wei Li1, Qingyong Ma1, Jiangbo Liu1, Liang Han1, Guodong Ma1, Han Liu1, Tao Shan1, Keping Xie2, Erxi Wu3

1Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, Shaanxi Province, China,2Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA,3Department of Pharmaceutical Sciences, NDSU, Sudro Hall 203, Fargo, ND 58105, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Diabetes and pancreatic cancer
4. Epithelial to mesenchymal transition (EMT)
5. EMT and cancer progression
6. EMT and high glucose
7. Hyperglycemia and oxidative stress
8. Oxidative stress, cancer metastasis and EMT
9. Diabetes and vascular destruction
10. Conclusions and future perspectives
11. Acknowlegements
12. References

1. ABSTRACT

As a vital step in the progression of cancer, metastasis poses the largest problem in cancer treatment and is the main cause of death of cancer patients. In pancreatic cancer, almost 80% of patients have locally deteriorated or metastatic disease and thus are not appropriate for resection at the time of diagnosis. Due to the high rate of incidence and mortality, it is crucial to study the molecular mechanisms of metastasis to clarify therapeutic targets to hinder the spread of cancer. Diabetes mellitus has long been considered a potential risk factor for pancreatic cancer. In this review, we comprehensively describe the role of hyperglycemia in governing critical steps of the metastatic process. In particular, we focus on the hyperglycemia-dependent aspects of the Epithelial-Mesenchymal Transition (EMT) and vascular dysfunction. Furthermore, we discuss how hyperglycemia-related production of reactive oxygen species (ROS) may play an important role in these two processes. A deep understanding of metastasis mechanisms will identify novel targets for therapeutic intervention.