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

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

Research output: Contribution to journalArticle

1043 Citations (Scopus)

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
StatePublished - Oct 27 2000
Externally publishedYes

Fingerprint

Matrix Metalloproteinases
Bone Marrow Cells
Skin
Bone
Carcinogenesis
Matrix Metalloproteinase 9
Keratinocytes
Oncogenes
Tumors
Neoplasms
Bone Marrow Transplantation
Macrophages
Epidermis
Mast Cells
Transgenic Mice
Neutrophils
Carcinoma
Incidence

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Coussens, L., Tinkle, C. L., Hanahan, D., & Werb, Z. (2000). MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell, 103(3), 481-490.

MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. / Coussens, Lisa; Tinkle, Christopher L.; Hanahan, Douglas; Werb, Zena.

In: Cell, Vol. 103, No. 3, 27.10.2000, p. 481-490.

Research output: Contribution to journalArticle

Coussens, L, Tinkle, CL, Hanahan, D & Werb, Z 2000, 'MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis', Cell, vol. 103, no. 3, pp. 481-490.
Coussens L, Tinkle CL, Hanahan D, Werb Z. MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell. 2000 Oct 27;103(3):481-490.
Coussens, Lisa ; Tinkle, Christopher L. ; Hanahan, Douglas ; Werb, Zena. / MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. In: Cell. 2000 ; Vol. 103, No. 3. pp. 481-490.
@article{442510bd27854ebeaa3d816ae8410a10,
title = "MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis",
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.",
author = "Lisa Coussens and Tinkle, {Christopher L.} and Douglas Hanahan and Zena Werb",
year = "2000",
month = "10",
day = "27",
language = "English (US)",
volume = "103",
pages = "481--490",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis

AU - Coussens, Lisa

AU - Tinkle, Christopher L.

AU - Hanahan, Douglas

AU - Werb, Zena

PY - 2000/10/27

Y1 - 2000/10/27

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0034721666&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034721666&partnerID=8YFLogxK

M3 - Article

C2 - 11081634

AN - SCOPUS:0034721666

VL - 103

SP - 481

EP - 490

JO - Cell

JF - Cell

SN - 0092-8674

IS - 3

ER -