Pancreatic cancer is the fourth leading cause of cancer-related death in both men and women and it is one ofthe most lethal malignancies with a 5-year survival rate of <5% and median survival duration of less than 6 months. In recent years there have been important advances in the understanding of the molecular biology of pancreatic cancer as well as in diagnosis, staging and treatment in patients with eariy stage tumor. However, minimal progress has been made in our understanding in progression and metastasis and treatment in patients with advanced disease. Recent reports and our preliminary data suggest that inflammation, tumorigenesis, and progression to metastasis are intimately linked in pancreatic cancer. Chronic inflammation can drive tumorigenesis, and tumors are inherently pro-inflammatory with infiltrating leukocytes thought critical for tumor maintenance and progression. Thus, molecules driving tumor-associated inflammation have considerable potential as therapeutic targets, yet this area remains relatively under-explored in pancreatic cancer. Chemokines are secreted proteins that regulate cell behavior via G-protein coupled receptors. Subsets of CC and CXC chemokines orchestrate tissue inflammation by recruiting and activating leukocytes and by regulating endothelial and epithelial cells. Constitutive expression of pro-inflammatory chemokines, a hallmark of many human cancers, helps establish a supportive tumor stroma and in some cases, directly stimulates tumor proliferation and invasion via receptors on tumor cells. Evidence suggests that CXCR2 regulates leukocytes, endothelial cells (ECs), and/or tumor cells and their precursors. To our knowledge, very little is known about the role of CXCR2 in de novo pancreatic cancer progression and metastasis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA163120-02
Application #
8555507
Study Section
Special Emphasis Panel (ZCA1-SRLB-3 (O1))
Project Start
2011-09-26
Project End
2016-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
2
Fiscal Year
2012
Total Cost
$179,085
Indirect Cost
$58,489
Name
University of Nebraska Medical Center
Department
Type
DUNS #
168559177
City
Omaha
State
NE
Country
United States
Zip Code
68198
Karmakar, Saswati; Seshacharyulu, Parthasarathy; Lakshmanan, Imayavaramban et al. (2017) hPaf1/PD2 interacts with OCT3/4 to promote self-renewal of ovarian cancer stem cells. Oncotarget 8:14806-14820
Shukla, Surendra K; Purohit, Vinee; Mehla, Kamiya et al. (2017) MUC1 and HIF-1alpha Signaling Crosstalk Induces Anabolic Glucose Metabolism to Impart Gemcitabine Resistance to Pancreatic Cancer. Cancer Cell 32:71-87.e7
Krishn, Shiv Ram; Kaur, Sukhwinder; Sheinin, Yuri M et al. (2017) Mucins and associated O-glycans based immunoprofile for stratification of colorectal polyps: clinical implication for improved colon surveillance. Oncotarget 8:7025-7038
Lakshmanan, Imayavaramban; Salfity, Shereen; Seshacharyulu, Parthasarathy et al. (2017) MUC16 Regulates TSPYL5 for Lung Cancer Cell Growth and Chemoresistance by Suppressing p53. Clin Cancer Res 23:3906-3917
Gebregiworgis, Teklab; Purohit, Vinee; Shukla, Surendra K et al. (2017) Glucose Limitation Alters Glutamine Metabolism in MUC1-Overexpressing Pancreatic Cancer Cells. J Proteome Res 16:3536-3546
Kaur, Sukhwinder; Smith, Lynette M; Patel, Asish et al. (2017) A Combination of MUC5AC and CA19-9 Improves the Diagnosis of Pancreatic Cancer: A Multicenter Study. Am J Gastroenterol 112:172-183
Joshi, Suhasini; Cruz, Eric; Rachagani, Satyanarayana et al. (2016) Bile acids-mediated overexpression of MUC4 via FAK-dependent c-Jun activation in pancreatic cancer. Mol Oncol 10:1063-77
Muniyan, Sakthivel; Haridas, Dhanya; Chugh, Seema et al. (2016) MUC16 contributes to the metastasis of pancreatic ductal adenocarcinoma through focal adhesion mediated signaling mechanism. Genes Cancer 7:110-124
Fink, Darci M; Steele, Maria M; Hollingsworth, Michael A (2016) The lymphatic system and pancreatic cancer. Cancer Lett 381:217-36
Huang, Huocong; Svoboda, Robert A; Lazenby, Audrey J et al. (2016) Up-regulation of N-cadherin by Collagen I-activated Discoidin Domain Receptor 1 in Pancreatic Cancer Requires the Adaptor Molecule Shc1. J Biol Chem 291:23208-23223

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