We propose to study lymphatic invasion and metastasis to lymph nodes, an early feature of metastasis of all adenocarcinomas. This proposal is to study the process of lymphatic invasion and metastasis in pancreatic cancer by undertaking both hypothesis-driven and hypothesis-generating specific aims.
The first aim, which is hypothesis driven, seeks to further invesfigate the role of Sonic Hedgehog (SHH) in tumor lymphangiogenesis and metastasis to lymph nodes. SHH is expressed in premalignant and malignant ductal epithelial cells of the pancreas, implicafing this morphogenic signaling protein in the inifiafion and progression of pancreafic cancer.
Aim 1 will build upon our recent published work [1] and other recent unpublished findings. We were the first to show that SHH contributes significantly to lymphangiogenesis by invesfigating the nature of paracrine signaling between pancreatic tumor cells producing SHH and lymphatic endothelial cells that are responding to SHH in the context of the emerging desmoplasfic reaction in pancreatic cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA163120-02
Application #
8555505
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
$173,571
Indirect Cost
$56,688
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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