Expression of integrins, degradative enzymes and their inhibitors in uveal melanoma: differences between in vitro and in vivo expression.
Posterior uveal melanoma is the most common intraocular malignancy in adults. Metastasis occurs in approximately 40% of all cases and spread is primarily to the liver. Once secondary hepatic disease has developed the prognosis is poor. Metastasis involves a series of adhesion and de-adhesion events, coupled with regulated tissue degradation to facilitate tumour cell invasion and spread to both local and distant sites. These processes are assisted by the expression of integrins and degradative enzymes by both tumour and host cells. Using a series of 10 uveal melanomas, we investigated the expression of a panel of integrins, degradative enzymes and their inhibitors that have been shown to be associated with metastasis. In addition, we undertook to establish if there might be differential expression in response to growth under artificial conditions. All the tumours expressed matrix metalloproteinases (MMP)-2 and-9, tissue inhibitor of metalloproteases (TIMP)-2, urokinase plasminogen activator (u-PA), plasminogen activator inhibitor (PAI)-1 and PAI-2. Differences in the expression of the integrins alpha1beta1, alpha2beta1 and alpha6beta1 were observed; in particular, these differences appeared to relate to expression as a consequence of growth in culture. In summary, uveal melanoma cells express both degradative enzymes and their respective inhibitors, which are important in metastasis. It would appear that differential expression of integrins is present, probably as a response to in vitro stimulation.
Baker
J K
JK
Institute for Cancer Studies, University of Sheffield, Medical School, Beech Hill Road, Sheffield, S10 2RX, UK.
Elshaw
S R
SR
Mathewman
G E
GE
Nichols
C E
CE
Murray
A K
AK
Parsons
M A
MA
Rennie
I G
IG
Sisley
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002448:Cell Adhesion; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000096:biosynthesis*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020784:Matrix Metalloproteinase 8 / Q000096:biosynthesis; D008545:Melanoma / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D017396:Plasminogen Activator Inhibitor 2 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis; D014604:Uveal Neoplasms / Q000378:metabolism*
D016023:Integrins; D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D019716:Tissue Inhibitor of Metalloproteinase-2; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8