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Aim 1 will build upon our recent published work [1] and other recent unpublished findings.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 #
5U54CA163120-05
Application #
8883407
Study Section
Special Emphasis Panel (ZCA1-SRLB-3)
Project Start
Project End
Budget Start
2015-08-01
Budget End
2016-07-31
Support Year
5
Fiscal Year
2015
Total Cost
$160,407
Indirect Cost
$52,389
Name
University of Nebraska Medical Center
Department
Type
DUNS #
168559177
City
Omaha
State
NE
Country
United States
Zip Code
68198
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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
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
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
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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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