Role of Activation Peptide of Procathepsin D in Proliferation and Invasion of Lung Cancer Cells

Abstract

Background: Procathepsin D (pCD) secreted by cancer cells, increases proliferation, metastasis and progression of breast cancer, however its role in lung cancer is still unclear. The purified pCD and its synthetic activation peptide (AP) have shown similar proliferative effect on various cancer cell lines. The aim of this study is to clarify the role of pCD and its AP in lung cancer by stable expression of pCD and pCD lacking its AP, in NCI-H23 lung cancer cells. Materials and Methods: The stable transfected clones were tested for cell proliferation, invasion and growth in nude mice. The effect of exogenous addition of purified pCD and its mutant proteins was also analyzed by proliferation assay. Results: The invasion and proliferation in vitro and tumor growth in vivo, demonstrated that the expression of pCD enhances the carcinogenic properties of NCI-H23 cells and that the AP is essential for these activities. Exogenous addition of purified proteins on various lung cancer cell lines showed that neither catalytic activity nor glycosylation are involved in the growth-promoting activity. Conclusion: This is the first report of pCD cDNA expression in lung cancer cells that enhances the growth and invasion of these cells both in vitro and in vivo.