Expression of membrane type 1 matrix metalloproteinase in papillomavirus-positive cells: role of the human papillomavirus (HPV) 16 and HPV8 E7 gene products.
Matrix metalloproteinases (MMPs) degrade extracellular matrix. They are involved in cellular proliferation, migration, angiogenesis, invasion and metastasis. MT-1 MMP, a membrane-bound MMP, is expressed in carcinomas of the uterine cervix in vivo. This type of cancer is associated with human papillomavirus (HPV) infection. Here it was shown that keratinocytes transformed with HPV16 or HPV18 in vitro, and HPV-positive cervical carcinoma cell lines, constitutively expressed MT-1 MMP. Expression of the E7 protein from the mucosal and cutaneous high-risk types HPV16 and HPV8, but not from the cutaneous low-risk type HPV1, was sufficient to induce MT-1 MMP expression in primary human keratinocytes and HaCaT cells. As a consequence, MMP-2 was activated. MT-1 MMP expression might play a role in the HPV life cycle by promoting proliferation of host cells and might contribute to their invasive phenotype during malignant progression.
Smola-Hess
Sigrun
S
Institute of Virology, University of Cologne, Fürst-Pückler-Str. 56, 50935 Cologne, Germany.
Pahne
Jenny
J
Institute of Virology, University of Cologne, Fürst-Pückler-Str. 56, 50935 Cologne, Germany.
Mauch
Cornelia
C
Department of Dermatology, University of Cologne, Joseph-Stelzmann-Str. 9, 50924 Cologne, Germany.
Zigrino
Paola
P
Department of Dermatology, University of Cologne, Joseph-Stelzmann-Str. 9, 50924 Cologne, Germany.
Smola
Hans
H
Department of Dermatology, University of Cologne, Joseph-Stelzmann-Str. 9, 50924 Cologne, Germany.
Pfister
Herbert J
HJ
Institute of Virology, University of Cologne, Fürst-Pückler-Str. 56, 50935 Cologne, Germany.
D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D015603:Keratinocytes / Q000821:virology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D027383:Papillomaviridae / Q000502:physiology*; D050725:Papillomavirus E7 Proteins
D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; C066076:oncogene protein E7, Human papillomavirus type 8; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2