Abstract
The matrix metalloproteinase MMP-9/gelatinase B is upregulated in angiogenic dysplasias and invasive cancers of the epidermis in a mouse model of multi-stage 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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Bone Marrow Cells / enzymology*
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Bone Marrow Transplantation
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Carcinoma, Squamous Cell / classification
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Carcinoma, Squamous Cell / metabolism
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Carcinoma, Squamous Cell / pathology*
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Cell Differentiation
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Cell Division
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Cell Transformation, Neoplastic / pathology*
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Disease Models, Animal
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Disease Progression
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Gene Deletion
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Gene Expression Regulation, Neoplastic
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Immunohistochemistry
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In Situ Hybridization
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Inflammation / enzymology
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Inflammation / pathology
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Keratinocytes / metabolism
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Keratinocytes / pathology
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Matrix Metalloproteinase 9 / deficiency
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Matrix Metalloproteinase 9 / genetics
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Matrix Metalloproteinase 9 / metabolism*
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Mice
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Mice, Knockout
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Mice, Transgenic
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Neoplasm Invasiveness
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Papillomaviridae / physiology
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Paracrine Communication
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Phenotype
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Skin Neoplasms / classification
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Skin Neoplasms / metabolism
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Skin Neoplasms / pathology*
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Stromal Cells / enzymology
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Stromal Cells / transplantation
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Up-Regulation
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X-Rays
Substances
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Matrix Metalloproteinase 9