MMP-9 Supplied by Bone Marrow-Derived Cells Contributes to Skin Carcinogenesis

Cell. 2000 Oct 27;103(3):481-90. doi: 10.1016/s0092-8674(00)00139-2.

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