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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZCA1)
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University of Nebraska Medical Center
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Roy, Sohini; Bag, Arup K; Dutta, Samikshan et al. (2018) Macrophage-Derived Neuropilin-2 Exhibits Novel Tumor-Promoting Functions. Cancer Res 78:5600-5617
Saxena, Sugandha; Purohit, Abhilasha; Varney, Michelle L et al. (2018) Semaphorin-5A maintains epithelial phenotype of malignant pancreatic cancer cells. BMC Cancer 18:1283
Barkeer, Srikanth; Chugh, Seema; Batra, Surinder K et al. (2018) Glycosylation of Cancer Stem Cells: Function in Stemness, Tumorigenesis, and Metastasis. Neoplasia 20:813-825
Saxena, Sugandha; Hayashi, Yuri; Wu, Lingyun et al. (2018) Pathological and functional significance of Semaphorin-5A in pancreatic cancer progression and metastasis. Oncotarget 9:5931-5943
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
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
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
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
Kumar, Sushil; Cruz, Eric; Joshi, Suhasini et al. (2017) Genetic variants of mucins: unexplored conundrum. Carcinogenesis 38:671-679
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

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