We herein investigated the potential role of
cathepsin L in lung
carcinogenesis.
Lung cancer cell lines and surgically resected
tumors were examined for the expression of the
cathepsin L protein and copy number alterations in its gene locus.
Cathepsin L was stably expressed in bronchiolar epithelial cells. Neoplastic cells expressed
cathepsin L at various levels, whereas its expression was completely lost in most of the
lung cancer cell lines (63.6%, 7/11) examined. Furthermore, expression levels were lower in a large fraction of lung
tumors (69.5%, 139/200) than in bronchiolar epithelia. The expression of
cathepsin L was lost in some
tumors (16.0%, 32/200). In
adenocarcinomas, expression levels were significantly lower in high-grade
tumors than in low-grade
tumors (one-way ANOVA, P < 0.0500). Copy number alterations were found in 18.0% (36 [32 gain + 4 loss] /200) of lung
tumors. No relationship existed between
cathepsin L protein expression levels and the copy number of its gene locus (Spearman's rank-order correlation, P = 0.3096). Collectively, these results suggest that the down-regulated expression of
cathepsin L, which is caused by an undefined mechanism other than copy number alterations, is involved in the progression of
lung adenocarcinomas.