This U54 application submitted in response to RFA CA10-021 Tumor Microenvironment (TMEN) is from the University of Nebraska Medical Center. The overall goal of this application is to define the role of interactions between pancreatic tumor cells and the tumor microenvironment during the development and progression of pancreatic cancer. A hallmark of pancreatic cancer is an extreme fibrotic response, and it is our collective hypothesis that fibrosis promotes signaling to the tumor cells, which promotes tumor growth, invasion and metastasis. Specifically, we will investigate interactions, regulation and contributio of secreted and cell surface molecules expressed by stromal cells, premalignant epithelial cells, and malignant cells. This project brings together investigators with experience in the biology of pancreatic cancer. The Pancreatic Tumor Microenvironment Network (TMEN) will include 4 research projects and 3 shared resources. Project 1: Interplay of tumor microenvironment and MUC4 in pancreatic cancer. Surinder K. Batra, Ph. D. Project 2: Lymphangiogeneis and metastasis during pancreatic cancer. Michael A. Hollingsworth, Ph. D Project 3: Role of N-cadherin in pancreatic tumor microenvironment. Keith Johnson, Ph.D. Project 4: CXCR2-dependent pancreatic cancer progression and metastasis. Rakesh K. Singh. Shared resource 1: Administrative Core;Shared resource 2: Rapid Autopsy Program (RAP) Core Shared resource 3: Genetically engineered Model (GEM) Core, Kay Wagner, Ph.D. The four research projects will investigate the role of microenvironment in the early stages of tumor development (Project 1), tumor progression (Projects 3 and 4) and angiogenesis and metastasis (Project 2). Together the group of investigators will exploit the powerful resources comprising of clinical samples, in vitro cell models and genetically engineered animal models of spontaneous tumorigenesis that exist at UNMC, to unravel the complex interplay between the components of tumor microenvironment and tumor cells in pancreatic cancer initiation and progression. With the expertise of the involved investigators in TME, we seek to improve our understanding of the underappreciated role of tumor microenvironment in pancreatic cancer and establish potential therapeutic relevance.

Public Health Relevance

There is increasing realization that microenvironment plays a critical role in pancreatic cancer (PC) progression. It is thus essential to understand how this nexus between the microenvironment and tumor cells operates during both early and late stages of tumorigenesis? The overall objective is to understand this complex interplay between the components of TME with tumor cells using cell models, clinical samples and genetically engineered animal models in PC.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
1U54CA163120-01
Application #
8212995
Study Section
Special Emphasis Panel (ZCA1-SRLB-3 (O1))
Program Officer
Mohla, Suresh
Project Start
2011-09-26
Project End
2016-07-31
Budget Start
2011-09-26
Budget End
2012-07-31
Support Year
1
Fiscal Year
2011
Total Cost
$831,601
Indirect Cost
Name
University of Nebraska Medical Center
Department
Biochemistry
Type
Schools of Medicine
DUNS #
168559177
City
Omaha
State
NE
Country
United States
Zip Code
68198
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