Matrix metalloproteinases (MMPs) are proteolytic enzymes that are implicated in multiple stages of cancer progression including invasion and metastasis. MMPs exert these effects by cleaving a diverse group of substrates, which include not only structural components of the extracellular matrix, but also growth factor receptors. By gelatin zymography we verified MMP activity in the pleural effusions of patients with benign and malignant disease. Of these patients, 32 had malignant pleural effusion, consisting of 20 breast cancer, 6 non-small cell lung carcinoma, 4 ovarian carcinoma, and 2 colonic adenocarcinoma, and 10 had benign pleural effusion (5 pleurisy and 5 cirrhosis). Zymography showed the constant presence of a substantial amount of MMP-2 in all samples analyzed, whereas MMP-9 was present to lesser quantities. MMP-2 activity was enhanced in pleural effusions from patients with benign diseases compared with cancer patients. MMP-9 was present in 59% of cancer patients and the lytic activity was enhanced in pleurisy and absent in cirrhosis. Furthermore, we determined the pleural effusion levels of the soluble extracellular domain of HER-2/neu. The levels of HER-2/neu ECD were above the cut-off value in breast cancer patients. No correlation between gelatinolytic activities and high HER-2/neu ECD values was found.

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