Distinct endobronchial expression of matrix-metalloproteinases (MMP) and their endogenous inhibitors in lung cancer

Background: Degradation of extracellular matrix (ECM) and basement membrane s is required for tumour cell invasion and metastasis. The ECM is degraded by matrix metalloproteinases (MMP) which are counteracted by tissue inhibit ors of metalloproteinases (TIMP). In aggressive tumours the balance of prot eolysis and antiproteolysis is disrupted, resulting in fast tumour progress ion and invasiveness. We examined A MMP and TIMP expression patterns in bro nchial washings of 58 consecutive lung tumour patients and 10 controls. Pat hohistological investigations revealed squamous cell carcinoma (n = 23), ad enocarcinoma (n = 18), small cell lung carcinoma (n = 9), and pulmonary met astases of extrapulmonary tumours (n = 8). MMP/TIMP expression n as correla ted to histology, location, or staging of rumours. Methods: Expression and activity of MMP was identified by zymography and We stern blotting. Expression of TIMP-1 and TIMP-2 was analysed by Western blo tting and enzyme-linked immunosorbent assays. Results: We identified MMP-1, MMP-2 and MMP-9, but not MMP-3 or MMP-8 in br onchial washings. All MMPs were expressed in the tumour-affected and the tu mour-free parts of the lung. While MMP-1 and MMP-9 vr;ere present in all sa mples, the inactive precursor of MMP-2 n as specifically expressed in adeno carcinoma or lung metastases of extrapulmonary tumours. No MMP-2 was found in controls. While TIMP-1 was expressed in all samples, TIMP-2 was not dete ctable. Conclusion: The tumour type-specific expression of the TIMP-2 precursor in adenocarcinoma and lung metastases suggests that MMP-1 in the absence of TI MP-2 correlates with aggressive tumour progression and may serve as an indi cator for poor prognosis.