Lymph node metastasis and the physicochemical micro-environment of pancreatic ductal adenocarcinoma xenografts
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Lise Mari K. Andersen1, Catherine S. Wegner1, Trude G. Simonsen1, Ruixia Huang1, Jon-Vidar Gaustad1, Anette Hauge1, Kanthi Galappathi1 and Einar K. Rofstad1
1Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
Einar K. Rofstad, email: firstname.lastname@example.org
Keywords: pancreatic carcinoma, metastasis, angiogenesis, hypoxia, interstitial fluid pressure
Received: December 02, 2016 Accepted: May 01, 2017 Published: May 26, 2017
Pancreatic ductal adenocarcinoma (PDAC) patients develop lymph node metastases early and have a particularly poor prognosis. The poor prognosis has been shown to be associated with the physicochemical microenvironment of the tumor tissue, which is characterized by desmoplasia, abnormal microvasculature, extensive hypoxia, and highly elevated interstitial fluid pressure (IFP). In this study, we searched for associations between lymph node metastasis and features of the physicochemical microenvironment in an attempt to identify mechanisms leading to metastatic dissemination and growth. BxPC-3 and Capan-2 PDAC xenografts were used as preclinical models of human PDAC. In both models, lymph node metastasis was associated with high IFP rather than high fraction of hypoxic tissue or high microvascular density. Seven angiogenesis-related genes associated with high IFP-associated lymph node metastasis were detected by quantitative PCR in each of the models, and these genes were all up-regulated in high IFP/highly metastatic tumors. Three genes were mutual for the BxPC-3 and Capan-2 models: transforming growth factor beta, angiogenin, and insulin-like growth factor 1. Further comprehensive studies are needed to determine whether there is a causal relationship between the up-regulation of these genes and high IFP and/or high propensity for lymph node metastasis in PDAC.
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