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Hofmann, UB; Eggert, AAO; Blass, K; Brocker, EB; Becker, JC.
Stromal cells as the major source for matrix metalloproteinase-2 in cutaneous melanoma.
Arch Dermatol Res. 2005; 297(4):154-160
Doi: 10.1007/s00403-005-0588-2
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- Co-Autor*innen der Med Uni Graz
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Becker Jürgen Christian
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- Abstract:
- Matrix metalloproteinases (MMPs) are essential for tumor progression, invasion and metastases formation. Expression of these proteinases is not only restricted to the tumor cells themselves, but also is found in normal stromal cells. Moreover, immunohistochemistry suggests stromal cells as the major source. To scrutinize this hypothesis we established a slowly growing, syngeneic tumor model using the B16-melanoma cell line B78D14. In vitro analysis demonstrated that B78D14 cells secreted MMP-2, MT1-MMP, and to a lesser degree MMP-9; in addition they expressed both MT1-MMP and EMMPRIN on their surface. In subcutaneous (s.c.) tumors of these cells MMP-2 expression was predominantly present at the tumor-stroma border indicating stromal cells as primary source for this protease in vivo. Indeed, double staining experiments and in situ zymography confirmed that tumor adjacent stromal cells at the invasive front expressed MMP-2 and only at this site activated MMP-2 was detectable. Notably, in an experimental pulmonary metastases model neither tumor nor stromal cells expressed MMP-2, suggesting that the capacity of stromal cells is largely dependent on the surrounding microenvironment.
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Animals -
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Antigens, CD147 - analysis Antigens, CD147 - genetics
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Cell Line, Tumor -
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Female -
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Gangliosides - analysis Gangliosides - genetics
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Gene Expression Regulation, Neoplastic -
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Humans -
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Immunohistochemistry -
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Matrix Metalloproteinase 2 - analysis Matrix Metalloproteinase 2 - genetics
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Matrix Metalloproteinases - analysis Matrix Metalloproteinases - genetics
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Melanoma - enzymology Melanoma - genetics Melanoma - pathology
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Mice -
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Mice, Inbred C57BL -
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Neoplasm Invasiveness -
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Skin Neoplasms - enzymology Skin Neoplasms - genetics Skin Neoplasms - pathology
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Stromal Cells - chemistry Stromal Cells - enzymology Stromal Cells - pathology
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Tissue Inhibitor of Metalloproteinases - analysis Tissue Inhibitor of Metalloproteinases - genetics
- Find related publications in this database (Keywords)
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matrix metalloproteinases
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melanoma
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stroma
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microenvironment
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tumor invasion