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
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, P.H.S.
MeSH terms
- Animals
- Bone Marrow Cells / enzymology*
- Bone Marrow Transplantation
- Carcinoma, Squamous Cell / classification
- Carcinoma, Squamous Cell / metabolism
- Carcinoma, Squamous Cell / pathology*
- Cell Differentiation
- Cell Division
- Cell Transformation, Neoplastic / pathology*
- Disease Models, Animal
- Disease Progression
- Gene Deletion
- Gene Expression Regulation, Neoplastic
- Immunohistochemistry
- In Situ Hybridization
- Inflammation / enzymology
- Inflammation / pathology
- Keratinocytes / metabolism
- Keratinocytes / pathology
- Matrix Metalloproteinase 9 / deficiency
- Matrix Metalloproteinase 9 / genetics
- Matrix Metalloproteinase 9 / metabolism*
- Mice
- Mice, Knockout
- Mice, Transgenic
- Neoplasm Invasiveness
- Papillomaviridae / physiology
- Paracrine Communication
- Phenotype
- Skin Neoplasms / classification
- Skin Neoplasms / metabolism
- Skin Neoplasms / pathology*
- Stromal Cells / enzymology
- Stromal Cells / transplantation
- Up-Regulation
- X-Rays
Substances
- Matrix Metalloproteinase 9