J. Yamashita et al., TUMOR NEUTROPHIL ELASTASE IS CLOSELY ASSOCIATED WITH THE DIRECT EXTENSION OF NONSMALL CELL LUNG-CANCER INTO THE AORTA, Chest, 111(4), 1997, pp. 885-890
Objective: Neutrophil elastase (NE) is the only neutral protease that
is able to degrade insoluble elastin and other extracellular matric; c
onstituents, and thus, may be involved in tumor invasion and metastasi
s. Using a highly specific and sensitive enzyme immunoassay (EIA), we
recently demonstrated that immunoreactive (ir)-NE is produced by non-s
mall cell lung cancer cell lines. We have measured the ir-NE concentra
tion in non-small cell lung cancer tumor extracts and have evaluated i
ts association with disease stage. Methods: We measured the ir-NE conc
entration in 144 non-small cell lung cancer tumor extracts using EIA,
which permits the rapid measurement of both the free and alpha(1)-prot
ease inhibitor (alpha 1-PI) complexed form of ir-NE. In 15 clinical T4
(cT4) patients, we also determined the concentration of free ir-NE in
tumor extracts using a kit that detects only NE complexed with alpha
1-PI and subtracting that value from the total NE concentration. Resul
ts: ir-NE was detected in tumor extracts from 115 of 144 patients, ran
ging from 0.21 to 23.35 mu g/100 mg protein, When the 144 specimens we
re grouped according to the clinical stage of disease, the ir-NE conce
ntration (mean +/- SE) was significantly higher in those with cT4 dise
ase (n = 15; 7.90 +/- 1.88 mu g/100 mg protein) than in those with cT1
(n = 29; 1.27 +/- 0.27; p<0.001), cT2 (n = 64; 1.18 +/- 0.17; p<0.001
), or cT3 disease (n = 26; 1.99 +/- 0.38; p<0.003). There was no signi
ficant association between the ir-NE concentration and cN-factor or an
y other clinical features, When the ir-NE concentration in the tumor e
xtracts of the cT4 patients was compared with respect to the tumor inv
asion sites, the ir-NE level was significantly higher in those with su
rgical T4 (sT4) disease with aortic invasion (n = 4; 17.4 +/- 3.10) th
an in those who were down-staged postoperatively (n = 5; 4.9 +/- 1.33;
p = 0.005) or those with sT4 disease with involvement of other sites
(n = 6; 4.07 +/- 1.83; p = 0.004). Similar results were observed for t
he free form of ir-NE. Conclusions: These data suggest that NE may be
involved in tumor progression of non-small cell lung cancer, Since the
aorta is one of the richest sources of polymeric and insoluble elasti
n, this enzyme may play an active role in the direct extension of the
tumor into the aorta.