PRODUCTION OF IMMUNOREACTIVE POLYMORPHONUCLEAR LEUKOCYTE ELASTASE IN HUMAN BREAST-CANCER CELLS - POSSIBLE ROLE OF POLYMORPHONUCLEAR LEUKOCYTE ELASTASE IN THE PROGRESSION OF HUMAN BREAST-CANCER

Breast cancer cells are known to express various proteolytic enzymes, which make them invasive and favour their dissemination to distant sites. However, it is unclear whether breast cancer cells have the ability to produce polymorphonuclear leucocyte elastase (PMN-E). We measured immunoreactive (ir) PMN-E content in the conditioned medium of two breast cancer cell lines, MCF-7 and ZR-75-1, and two normal breast epithelial cell lines, HBL-100 and Hs 578Bst, using a highly specific and sensitive enzyme immunoassay. Furthermore, ir-PMN-E content was determined in tissue extracts from 62 human breast cancers. ir-PMN-E content in the culture medium of MCF-7 cells and ZR-75-1 cells increased as a function of lime, regardless of the presence or absence of oestradiol. On the other hand, no detectable ir-PMN-E was secreted into the culture medium of HBL-100 and Hs 578Bst cells. ir-PMN-E was detectable in 59 of 62 tissue extracts prepared from human breast cancers, the concentration ranging from 0.12 to 19.17 mu g per 100 mg of protein. When 62 breast cancer specimens were categorised into four groups in terms of clinical stage, ir-PMN-E content in breast cancer tissue was significantly higher in stage III (8.90 +/- 5.13 mu g 100 mg(-1) protein) and stage IV (12.19 +/- 5.44 mu g 100 mg(-1) protein) patients than in stage I (1.64 +/- 1.54 mu g 100 mg(-1) protein) and stage II (4.23 +/- 3.74 mu g 100 mg(-1) protein) patients. Breast cancer patients with high levels of ir-PMN-E showed significantly shorter disease-free survival and overall survival than those with low levels of ir-PMN-E at the cut-off point of 8.99 mu g 100 mg(-1) protein. In the multivariate analysis, ir-PMN-E content was found to be a significant prognostic factor for disease recurrence and death in human breast cancer.