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Sci Rep DOI:10.1038/srep40495

Quantitative proteomic profiling of the extracellular matrix of pancreatic islets during the angiogenic switch and insulinoma progression.

Publication TypeJournal Article
Year of Publication2017
AuthorsNaba, A, Clauser, KR, Mani, DR, Carr, SA, Hynes, RO
JournalSci Rep
Volume7
Pages40495
Date Published2017 Jan 10
ISSN2045-2322
Abstract

The angiogenic switch, the time at which a tumor becomes vascularized, is a critical step in tumor progression. Indeed, without blood supply, tumors will fail to grow beyond 1 mm(3) and are unlikely to disseminate. The extracellular matrix (ECM), a major component of the tumor microenvironment, is known to undergo significant changes during angiogenesis and tumor progression. However the extent of these changes remains unknown. In this study, we used quantitative proteomics to profile the composition of the ECM of pancreatic islets in a mouse model of insulinoma characterized by a precisely timed angiogenic switch. Out of the 120 ECM proteins quantified, 35 were detected in significantly different abundance as pancreatic islets progressed from being hyperplastic to angiogenic to insulinomas. Among these, the core ECM proteins, EFEMP1, fibrillin 1, and periostin were found in higher abundance, and decorin, Dmbt1, hemicentin, and Vwa5 in lower abundance. The angiogenic switch being a common feature of solid tumors, we propose that some of the proteins identified represent potential novel anti-angiogenic targets. In addition, we report the characterization of the ECM composition of normal pancreatic islets and propose that this could be of interest for the design of tissue-engineering strategies for treatment of diabetes.

DOI10.1038/srep40495
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/28071719?dopt=Abstract

Alternate JournalSci Rep
PubMed ID28071719
PubMed Central IDPMC5223159
Grant ListP30 CA014051 / CA / NCI NIH HHS / United States
U54 CA126515 / CA / NCI NIH HHS / United States
U54 CA163109 / CA / NCI NIH HHS / United States