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

ABSTRACT: Naba A, Clauser KR, Mani DR, Carr SA, Hynes RO. The angiogenic switch, the time at which a tumor becomes vascularized, is a critical step in tumor progression. Indeed, it has been demonstrated that without blood supply, tumors will fail to grow beyond 1mm3 and are unlikely to disseminate. The extracellular matrix (ECM), a major component of the tumor microenvironment, is known to undergo significant changes during tumor progression and, in particular, during angiogenesis. However the extent of these changes remains unknown. In this study, we used quantitative proteomics to characterize the composition of the ECM of pancreatic islets in a transgenic 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 during tumor progression. 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 here the characterization of the ECM composition of normal pancreatic islets and propose that this could be of interest for the design of tissue engineering and regenerative strategies for treatment of diabetes.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Steven A. Carr

PROVIDER: MSV000080124 | MassIVE |

SECONDARY ACCESSION(S): PXD005608

REPOSITORIES: MassIVE

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