Expression of matrix metalloproteinase (MMP)-2, MMP-9, MMP-13, and MT1-MMP in skin tumors of human papillomavirus type 8 transgenic mice.
Human papillomaviruses (HPV) are small DNA viruses that induce a wide variety of hyperproliferative lesions in cutaneous and mucosal epithelia. It is proposed that HPV is involved in non-melanoma skin cancer development. We have previously shown that HPV8 transgenic mice spontaneously develop papillomatous skin tumors. Histology revealed epidermal hyperplasia, acanthosis and hypergranulosis and in some cases squamous cell carcinomas (SCC). Zymographic and immunoblot analysis of normal skin extracts identified increased amounts of matrix metalloproteinase (MMP)-9, MMP-13 and MT1-MMP in HPV8-positive mice compared with HPV8-negative animals. In situ gelatin zymography of tumor specimens displayed a strong proteolytic activity in papillomas, and SCC putatively attributed to the increased amounts of activated MMP-9 found in tissue extracts. In addition, immunoblot analysis revealed increased amounts of active MMP-13 and MT1-MMP in tumor extracts as compared with control extracts. Immunohistochemical stainings of SCC specimens depicted MMP-13 to be specifically expressed in stromal fibroblasts neighboring the tumor islands, whereas MT1-MMP was detected both in tumor cells and in stromal cells. Taken together, these results implicate a role for MMPs in the development of HPV8-induced cutaneous tumors.
Akgül
Baki
B
Institute of Virology, University of Cologne, Germany. baki.akguel@web.de
Pfefferle
Regina
R
Marcuzzi
Gian Paolo
GP
Zigrino
Paola
P
Krieg
Thomas
T
Pfister
Herbert
H
Mauch
Cornelia
C
D000818:Animals; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D017364:Collagenases / Q000378:metabolism; D053509:Matrix Metalloproteinase 13; D053511:Matrix Metalloproteinase 14; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D051379:Mice; D008822:Mice, Transgenic; D027383:Papillomaviridae; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
C507096:Mmp14 protein, mouse; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; C507081:Mmp13 protein, mouse; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D053511:Matrix Metalloproteinase 14