Secretory Leukocyte Protease Inhibitor in Cancer Development

: Secretory leukocyte protease inhibitor (SLPI), an epithelial‐specific serine protease inhibitor of the whey acidic protein (WAP) family, exerts broad tissue‐protective functions: on the one hand, it counteracts inflammatory responses and invading pathogens, and on the other hand, it repairs the damaged tissue. Here, we report that subcutaneous in vivo passage of low‐malignant 3LL‐S cells increases the malignancy of these cancer cells. Applying the subtraction suppressive hybridization method to this cancer model, we identify SLPI as one of the genes whose level of expression directly correlates with the malignancy of the cancer cells. Using transfection experiments, we demonstrate that overexpression of mouse or human SLPI in 3LL‐S cells is sufficient to enhance their malignant behavior, and that this activity of SLPI is related to its ability to inhibit serine proteases. Furthermore, using cDNA dot‐blot hybridization, we show that in human gynecological cancer tissue SLPI expression is frequently increased as compared with normal tissue. This study underscores the promalignant role of SLPI in the development of cancer and its potential usefulness as a biomarker for gynecological cancer.