MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis

Lisa M. Coussens, Christopher L. Tinkle, Douglas Hanahan, Zena Werb

Research output: Contribution to journalArticle

1059 Scopus citations

Abstract

The matrix metalloproteinase MMP-9/gelatinase B is upregulated in angiogenic dysplasias and invasive cancers of the epidermis in a mouse model of multistage tumorigenesis elicited by HPV16 oncogenes. Transgenic mice lacking MMP-9 show reduced keratinocyte hyperproliferation at all neoplastic stages and a decreased incidence of invasive tumors. Yet those carcinomas that do arise in the absence of MMP-9 exhibit a greater loss of keratinocyte differentiation, indicative of a more aggressive and higher grade tumor. Notably, MMP-9 is predominantly expressed in neutrophils, macrophages, and mast cells, rather than in oncogene-positive neoplastic cells. Chimeric mice expressing MMP-9 only in cells of hematopoietic origin, produced by bone marrow transplantation, reconstitute the MMP-9-dependent contributions to squamous carcinogenesis. Thus, inflammatory cells can be coconspirators in carcinogenesis.

Original languageEnglish (US)
Pages (from-to)481-490
Number of pages10
JournalCell
Volume103
Issue number3
DOIs
StatePublished - Oct 27 2000

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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