Induction of neutrophil elastase by TNF-α in human cancer cell lines

Similarities between cancer cells and neutrophil, such as circulating by single cells, attachment to the vascular system of the target and invasion into the target, lead to a hypothesis that cancer cells might produce neutrophil elastase or a very similar protease. Although the production of immunoreactive polymorphonuclear leukocyte elastase (ir-PMN-E) can be measured by enzyme immunoassay (EIA) in human cancer and cancer cell lines, we were having difficulty to detect this at mRNA level. TNF-alpha stimulation induces neutrophil elastase to a detectable level by RT-PCR in human cancer cell lines. In SUIT2, neutrophil elastase mRNA was detectable from 0.1 ng/ml of TNF-alpha stimulation which in EBC1 and MCF7 requires 1.0 ng/ml of TNF-alpha. For PC-3, there was no induction. The RTPCR direct sequencing method revealed that the induced neutrophil elastase has no mutation. Although the amount of this molecule is low, as neutrophil elastase is a protease, the function in living systems does not depend on their amount but mainly on the activity they display. The result of this study indicates that some of the cancer cells could produce neutrophil elastase by stimulation of TNF-alpha and also suggests that neutrophil elastase produced by cancer cells is involved in clinical aspects of malignancy under inflammatory conditions. (C) 2003 Elsevier B.V. All rights reserved.