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Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12493-8. Epub 2006 Aug 4.

Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis.

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  • 1Diabetes and Comprehensive Cancer Centers, University of California, San Francisco, CA 94143, USA.

Abstract

Matrix metalloprotease type 9 (MMP-9) has been functionally implicated in VEGF activation, the induction and maintenance of chronic angiogenesis, and early stage tumor growth in a number of mouse models of cancer. In this article, we have identified two inflammatory cell types that are major sources of MMP-9 in the angiogenic stages of pancreatic islet carcinogenesis that unfold in RIP1-Tag2 transgenic mice. MMP-9-expressing neutrophils were predominantly found inside angiogenic islet dysplasias and tumors, whereas MMP-9-expressing macrophages were localized along the periphery of such lesions. Transient depletion of neutrophils significantly suppressed VEGF:VEGF-receptor association, a signature of MMP-9 activity, and markedly reduced the frequency of initial angiogenic switching in dysplasias. Thus infiltrating neutrophils can play a crucial role in activating angiogenesis in a previously quiescent tissue vasculature during the early stages of carcinogenesis.

PMID:
16891410
[PubMed - indexed for MEDLINE]
PMCID:
PMC1531646
Free PMC Article
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