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.
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.
|Macha, M A; Rachagani, S; Pai, P et al. (2015) MUC4 regulates cellular senescence in head and neck squamous cell carcinoma through p16/Rb pathway. Oncogene 34:1698-708|
|Wakaskar, Rajesh R; Bathena, Sai Praneeth R; Tallapaka, Shailendra B et al. (2015) Peripherally cross-linking the shell of core-shell polymer micelles decreases premature release of physically loaded combretastatin A4 in whole blood and increases its mean residence time and subsequent potency against primary murine breast tumors after I Pharm Res 32:1028-44|
|Zhu, Yu; Li, Jing; Kanvinde, Shrey et al. (2015) Self-immolative polycations as gene delivery vectors and prodrugs targeting polyamine metabolism in cancer. Mol Pharm 12:332-41|
|Vaz, A P; Ponnusamy, M P; Rachagani, S et al. (2014) Novel role of pancreatic differentiation 2 in facilitating self-renewal and drug resistance of pancreatic cancer stem cells. Br J Cancer 111:486-96|
|Joshi, Suhasini; Kumar, Sushil; Choudhury, Amit et al. (2014) Altered Mucins (MUC) trafficking in benign and malignant conditions. Oncotarget 5:7272-84|
|Souchek, J J; Baine, M J; Lin, C et al. (2014) Unbiased analysis of pancreatic cancer radiation resistance reveals cholesterol biosynthesis as a novel target for radiosensitisation. Br J Cancer 111:1139-49|
|Kaur, Sukhwinder; Sharma, Neil; Krishn, Shiv Ram et al. (2014) MUC4-mediated regulation of acute phase protein lipocalin 2 through HER2/AKT/NF-*B signaling in pancreatic cancer. Clin Cancer Res 20:688-700|
|Liu, Xiang; Yi, Chunhui; Wen, Yunfei et al. (2014) Interactions between MUC1 and p120 catenin regulate dynamic features of cell adhesion, motility, and metastasis. Cancer Res 74:1609-20|
|Momi, Navneet; Kaur, Sukhwinder; Rachagani, Satyanarayana et al. (2014) Smoking and microRNA dysregulation: a cancerous combination. Trends Mol Med 20:36-47|
|Stark, Jaime L; Mehla, Kamiya; Chaika, Nina et al. (2014) Structure and function of human DnaJ homologue subfamily a member 1 (DNAJA1) and its relationship to pancreatic cancer. Biochemistry 53:1360-72|
Showing the most recent 10 out of 28 publications