Elafin, an inhibitor of elastase, is a prognostic indicator in breast cancer

Panels of normal and immortalized breast epithelial cells, along with breast carcinoma cells, were used to examine the impact of adenoviral-mediated elafin expression or shRNA-mediated inhibition of elastase on the growth of cells and xenografts in nude mice. To determine the prognostic significance of decreased elafin in patients with invasive breast cancer, previously published gene array datasets were interrogated.Elafin expression had no effect on non-tumorigenic cells but resulted in marked inhibition of cell growth in breast cancer cell lines. Control-treated xenografts generated a tumor burden that necessitated sacrifice within one month of initial treatment, whereas xenograft-bearing mice treated with Ad-Elafin were alive at eight months with marked reduction in tumor growth. Elastase inhibition mimicked these results, showing decreased tumor cell growth in vitro and in vivo. Low expression of elafin gene correlated with significantly reduced time to relapse, and when combined with high expression of elastase gene was associated with decreased survival in breast cancer patients.Our data suggest that elafin plays a direct role in the suppression of tumors through inhibition of elastase and thus serves as a prognostic indicator for breast cancer patients.Polymorphonuclear leukocyte elastase (hereafter referred to as elastase) disintegrates matrix proteins [1], implicating this enzyme in breast cancer cell invasion and metastasis. Elastase is produced by neutrophils and also by human breast cancer cells but not by normal breast epithelial cells in culture [2]. Increased levels of elastase have been shown to be strongly associated with recurrence and death in breast cancer patients [3]. A study of 313 breast cancer patients with a median of 18.5 years of follow-up showed that elastase in tumor extracts was an independent prognostic factor associated with increased risk of recurrence [4]. These studies suggest that elastase could have a role in tumor progression