Differential expression of tissue inhibitor of metalloproteinases-2 by cutaneous squamous and basal cell carcinomas.
Tumor cell invasion and metastasis are considered to represent a multistep process leading to the degradation of the extracellular matrix by proteolytic enzymes. The functional activity of matrix metalloproteinases (MMPs) is controlled by tissue inhibitor of metalloproteinases-2 (TIMP-2), which has been shown to inhibit tumor cell invasion and metastasis in vitro and in vivo. To assess the role of TIMP-2 in skin-derived epithelial tumors, we have analyzed the expression of TIMP-2 mRNA in primary tissue samples from human cutaneous basal (BCC) and squamous cell carcinoma (SCC) for a correlation with their different invasive and metastatic potential. Comparative quantitative analysis of TIMP-2 mRNA levels by Northern blot hybridization demonstrated significantly higher TIMP-2 tissue levels in BCC than in SCC, indicating an inverse correlation between TIMP-2 expression and the metastatic capacity of these tumors in vivo. By in situ hybridization, tumor stromal cells were identified as the principal source of TIMP-2 mRNA in both BCC and SCC. A comparable distribution has been reported previously for several matrix metalloproteinases in cutaneous BCC and SCC, indicating co-localization of metalloproteinases with their respective inhibitor. These results may suggest that TIMP-2 substantially contributes to the biological behavior of epithelium-derived skin tumors by significantly inhibiting tumor cell metastasis.
Wagner
S N
SN
Department of Dermatology, University of Essen, Germany.
Ockenfels
H M
HM
Wagner
C
C
Soyer
H P
HP
Goos
M
M
D002280:Basal Cell Carcinoma / Q000737:chemistry / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D011480:Protease Inhibitors / Q000378:metabolism; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000737:chemistry; D012878:Skin Neoplasms / Q000737:chemistry / Q000235:genetics*; D019716:Tissue Inhibitor of Metalloproteinase-2; D014158:Transcription, Genetic
D011480:Protease Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2