Local increase in polymorphonuclear leukocyte elastase is associated with tumor invasiveness in non-small cell lung...

The production of tumor cell proteases is implicated in tumor cell invasion and metastasis. To determine whether lung cancer cells can produce polymorphonuclear leukocyte elastase (PMN-E), we measured the concentration of immunoreactive (ir)-PMN-E in the conditioned medium of seven lines of non-small cell lung cancer cells, EBC-1, LC-1sq, LK-2, A-549, 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 developed enzyme immunoassay (EIA). We measured the concentration of ir-PMN-E in extracts of 40 non-small cell lung cancers, and evaluated its association with the clinicopathologic findings in these patients. The ir-PMN-E level in the culture medium increased with time in six of the seven 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 normal 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 micrograms/100 mg of protein. When 40 specimens of lung cancer were categorized by clinical stage of disease, the ir-PMN-E concentration was significantly 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 significantly higher in T3 and T4 tumors than in T1 or T2 tumors. Analysis of prognostic factors in a group of 101 patients with non-small cell lung cancer demonstrated that those with high ir-PMN-E had a significantly shorter overall survival vs those with a low ir-PMN-E at the cutoff point of 3.5 micrograms/100 mg of protein. Multivariate analysis showed that ir-PMN-E was a significant porgnostic factor for early death (hazard ratio, 4.04; 95% confidence interval, 1.65 to 9.95) (p = 0.005), suggesting it was an independent marker for prognosis. Results suggest that the local production of PMN-E may be involved in the tumor invasion associated with a poor prognosis in patients with non-small cell lung cancer.