LOCAL INCREASE IN POLYMORPHONUCLEAR LEUKOCYTE ELASTASE IS ASSOCIATED WITH TUMOR INVASIVENESS IN NON-SMALL-CELL LUNG-CANCER

The production of tumor cell proteases is implicated in tumor cell inv asion and metastasis. To determine whether lung cancer cells can produ ce polymorphonuclear leukocyte elastase (PMN-E), we measured the conce ntration of immunoreactive (ir)-PMN-E in the conditioned medium of sev en lines of non-small cell lung cancer cells, EBC-1, LC-1sq, LK-2, A-5 49, PC-3, RERF-LC-MS, and RERF-LC-OK, and three normal lung epithelial cell lines, CCD-8Lu, WI-1003, and LL-24, by using a recently develope d enzyme immunoassay (EW). We measured the concentration of ir-PMN-E i n extracts of 40 non-small cell lung cancers, and evaluated its associ ation with the clinicopathologic findings in these patients, The ir-PM N-E level in the culture medium increased with time in six of the seve n lines of lung cancer cells; the exception was PC-3, No detectable ir -PMN-E was secreted into the culture medium of the three lines of norm al lung epithelial cells. The ir-PMN-E was detected in tissue extracts from 34 to 40 specimens at concentrations ranging from 0.11 to 15.5 m u g/100 mg of protein. When 40 specimens of lung cancer were categoriz ed by clinical stage of disease, the ir-PMN-E concentration was signif icantly higher in stage IIIB vs stages I, II, or IIIA. Similarly, the ir-PMN-E concentration was significantly higher in stage IIIA than in stage I. Evaluation of correlations between the ir-PMN-E concentration and patient characteristics showed that the ir-PMN-E level was signif icantly higher in T3 and T4 tumors than in T1 or T2 tumors. Analysis o f prognostic factors in a group of 101 patients with non-small cell lu ng cancer demonstrated that those with a high ir-PMN-E had a significa ntly shorter overall survival vs those with a low ir-PMN-E at the cuto ff point of 3.5 mu g/100 mg of protein. Multivariate analysis showed t hat ir-PMN-E was a significant prognostic factor for early death (haza rd ratio, 4.04; 95% confidence interval, 1.65 to 9.95) (p=0.005), sugg esting it was an independent marker for prognosis. Results suggest tha t the local production of PMN-E may he involved in the tumor invasion associated with a poor prognosis in patients with non-small cell lung cancer.