Vashishta Aruna, Ohri Sujata Saraswat, Proctor Mary, Fusek Martin, Vetvicka Vaclav
Department of Pathology, University of Louisville, Louisville, KY 40218, USA.
Anticancer Res. 2006 Nov-Dec;26(6B):4163-70.
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 ofpCD and its AP in lung cancer by stable expression of pCD and pCD lacking its AP, in NCI-H23 lung cancer cells.
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.
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.
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.
癌细胞分泌的组织蛋白酶D前体(pCD)可促进乳腺癌的增殖、转移和进展,但其在肺癌中的作用仍不清楚。纯化的pCD及其合成激活肽(AP)对多种癌细胞系显示出相似的增殖作用。本研究旨在通过在NCI-H23肺癌细胞中稳定表达pCD和缺失AP的pCD,阐明pCD及其AP在肺癌中的作用。
对稳定转染的克隆进行细胞增殖、侵袭及在裸鼠体内生长的检测。还通过增殖试验分析了外源性添加纯化的pCD及其突变蛋白的作用。
体外侵袭与增殖及体内肿瘤生长表明,pCD的表达增强了NCI-H23细胞的致癌特性,且AP对这些活性至关重要。在多种肺癌细胞系上外源性添加纯化蛋白表明,生长促进活性既不涉及催化活性也不涉及糖基化。
这是关于pCD cDNA在肺癌细胞中表达的首次报道,该表达增强了这些细胞在体外和体内的生长及侵袭能力。