Profiling of extracellular matrix proteins in pancreatic ductal adenocarcinoma progression and metastasis

Tian, C. X., Ohlund, D., Clauser, K., Carr, S. A., Tuveson, D. A., Hynes, R. O. (2015) Profiling of extracellular matrix proteins in pancreatic ductal adenocarcinoma progression and metastasis. Cancer Research, 75 (Supple). ISSN 0008-5472

URL: http://cancerres.aacrjournals.org/content/75/15_Su...
DOI: 10.1158/1538-7445.am2015-1819

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most common causes of cancer-related death, and is characterized by accumulation of excessive extracellular matrix (ECM). Although the ECM of tumors, such as PDAC, has long been known to have major effects on behavior of both tumor and stromal cells, including invasion, angiogenesis, metastasis, and resistance to therapy, the detailed composition of the ECM in PDAC tumor progression and metastasis are not understood. To study the involvement of ECM proteins in PDAC primary tumor growth and the tissue-specific metastasis program, we modified the comprehensive ECM proteomic approach by Mass Spectrometry (MS) recently developed in our lab to profile the ECM changes during PDAC progression in both the LSL-KrasG12D/+; LSL-Trp53R127H/+; Pdx-1-Cre (KPC) mouse models of PDAC and human patient samples. We will compare ECM profiles from normal pancreas, pancreatitis, early and late pancreatic intraepithelial neoplasia (PanIN) stages, and PDAC. Initial MS identified between 100 and 140 ECM proteins in samples representing each stage. The changes identified include changes previously associated with PDAC (e.g., upregulation of Tnc, Lox) plus novel, previously unreported changes. The combination of mouse models and human samples will allow us to uncover critical ECM changes during PDAC progression and metastasis and, furthermore, to investigate and understand the functional consequences of such changes. The ongoing studies will characterize the ECM of PDAC in detail and provide novel insights into diagnosis, prognosis and treatments of this very difficult disease.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > extracellular matrix proteins
diseases & disorders > cancer > metastasis
diseases & disorders > cancer > cancer types > pancreatic cancer
CSHL Authors:
Communities: CSHL labs > Tuveson lab
Depositing User: Matt Covey
Date Deposited: 01 Apr 2016 20:50
Last Modified: 01 Apr 2016 20:50
URI: http://repository.cshl.edu/id/eprint/32469

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