Cysteine proteinase cathepsin H in tumours and sera of lung cancer patients: relation to prognosis and cigarette smoking

Abstract

Summary In order to evaluate the role of cysteine peptidase cathepsin H (Cath H) in human lung cancer its protein levels were determined in 148 pairs of lung tumour tissue and adjacent non-tumourous lung parenchyma using the enzyme-linked immunosorbent assay technique. Additionally, Cath H levels were determined in sera of 171 patients with malignant tumours, 34 patients with benign lung diseases and 47 healthy controls. The median level of Cath H in tumour tissue was 0.64 times that in the corresponding lung parenchyma. Relating tumour levels with histological type we found higher Cath H levels in small-cell and adenocarcinomas and lower levels in squamous cell carcinoma, large-cell carcinoma and secondary tumours. A significant difference in Cath H level between lung tumour tissue and non-tumourous lung parenchyma was associated with the group of cigarette smokers (156 vs 263 ng mg -1 protein, P < 0.001). For this group of patients Cath H tumour levels correlated with the survival rate, while for the entire patient population this was not the case. Smokers with high tumour levels of Cath H experienced poor survival. Cath H was significantly higher in sera of patients with malignant and benign lung diseases than in control sera (P < 0.001). The increase was significant for all histological types, being the highest in small-cell and squamous cell carcinomas. Our study reveals that in lung tumours there is different behaviour of Cath H compared with other cysteine peptidases, e.g. cathepsin B and cathepsin L. Variations between tissue and serum levels of Cath H indicate either reduced expression or enhanced secretion of this enzyme in lung tumours.

Mouse Models of Human Non-Small-Cell Lung Cancer: Raising the Bar

“…2) (Grimm et al 2005). Cathepsin proteases are also overexpressed in some patients with lung cancer, and their expression has been associated with tumor invasion and poor prognosis (Schweiger et al 2000;Joyce et al 2004). It remains to be determined whether these molecules will be useful in imaging human tumors, but this work highlights the feasibility of using gene expression profiling to identify molecular targets for imaging lung cancer.…”

Use of gene expression profiling to direct in vivo molecular imaging of lung cancer

“…Similar results have been reported in patients with lung adenocarcinoma. For example, cathepsin H is overexpressed at the RNA and protein levels in normalappearing lung adjacent to lung adenocarcinomas (15). Because cathepsin protease activity appears increased in the tumor as well as the adjacent normal-appearing lung, this finding raises a potential paradox of why the signal is higher in areas with tumors.…”

“…Recently, cathepsin B was also found to be a predictor of prostate cancer that extends beyond the prostate gland (24). Many human lung adenocarcinomas also have been found to overexpress cathepsin H (15,25). Cathepsin L has been reported to be an independent prognostic factor for poor outcome in some studies (22) but not in others (20,23).…”

“…These proteases are also overexpressed in some patients with lung cancer, and their expression has been associated with tumor invasion and poor prognosis (14,15). We hypothesized that tumor protease activity could be used as a means of detecting these tumors.…”

Subcloning and Expression of Functional Human Cathepsin B and K in E. coli: Characterization and Inhibition by Flavonoids

“…and have been linked to many types of cancer including melanoma (Matarrese et al, 2010;Quintanilla-Dieck et al, 2008), hepatocellular carcinoma (Leto et al, 1997;Leto et al, 1996), breast cancer (Foekens et al, 1998;Laurent-Matha et al, 1998;Masson et al, 2011;Vashishta et al, 2007), lung cancer (Ledakis et al, 1996;Schweiger et al, 2000), prostate cancer (Brubaker et al, 2003;Kishore Kumar et al, 2010;Podgorski et al, 2009;Podgorski et al, 2007;Steffan et al, 2010), nasopharyngeal cancer (Cheng et al, 2008;Xu et al, 2009), thyroid cancer (Mikosch et al, 2008;Tedelind et al, 2010), bone cancer Podgorski et al, 2007) as well as osteoporosis (Bone et al, 2010;Deal, 2009;Stoch and Wagner, 2007;Yasuda et al, 2005), rheumatoid arthritis (Skoumal et al, 2005;Skoumal et al, 2008), Alzheimer's Disease (Hook et al, 2007;Hook et al, 2009;Urbanelli et al, 2008), cardiovascular disease (Bengtsson et al, 2008;Lutgens et al, 2007), and obesity (Li et al, 2010;Naour et al, 2010;Podgorski et al, 2007;Yang et al, 2008).…”