Cathepsin S in tumours, regional lymph nodes and sera of patients with lung cancer: relation to prognosis

Cysteine proteinase cathepsin S (Cat S) is expressed mainly in lymphatic tissues and has been characterised as a key enzyme in major histocompatibility complex class II (MHC-II) mediated antigen presentation. Cat S has been measured in tissue cytosols of lung parenchyma, lung tumours and lymph nodes and in sera of patients with lung tumours and of healthy controls, by specific enzyme-linked immunosorbent assay (ELISA). A difference in Cat S level was found between tumour and adjacent control tissue cytosols of 60 lung cancer patients (median 4.3 vs. 2.8 ng mg–1protein). In lymph nodes obtained from 24 patients of the same group, the level of Cat S was significantly higher than in tumours or lung parenchyma (P< 0.001). Additionally, significantly higher levels were found in non-infiltrated than in infiltrated lymph nodes (median 16.6 vs 7.5 ng mg–1protein). Patients with low levels of Cat S in tumours and lung parenchyma exhibited a significantly higher risk of death than those with high levels of Cat S (P= 0.025 – tumours;P= 0.02 – parenchyma). Immunohistochemical analysis (IHA) of lung parenchyma revealed a staining reaction in alveolar type II cells, macrophages and bronchial epithelial cells. In regional lymph node tissue, strong staining of Cat S was found in lymphocytes and histiocytes. Nevertheless, Cat S was detected also in tumour cells, independently of their origin. Our results provide evidence that Cat S may be involved in malignant progression. Its role, however, differs from that of the related Cats B and L and could be associated with the immune response rather than with remodelling of extracellular matrix. © 2001 Cancer Research Campaign http://www.bjcancer.com

• Publication year

  2001

• Venue

  British Journal of Cancer

• Publication date

  2001-10-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1054/bjoc.2001.2057PMID 11710834PMCID 2375152
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Immunochemical Localisation of Cathepsin S, Cathepsin L and MHC Class II-Associated p41 Isoform of Invariant Chain in Human Lymph Node Tissue

  2001cited by this paper
• Antigen-processing machinery breakdown and tumor growth.

  2000cited by this paper
• Cathepsin B in infiltrated lymph nodes is of prognostic significance for patients with nonsmall cell lung carcinoma

  2000cited by this paper
• Fluorometric Microassays for the Determination of Cathepsin L and Cathepsin S Activities in Tissue Extracts

  1999cited by this paper
• Crystal structure of MHC class II‐associated p41 Ii fragment bound to cathepsin L reveals the structural basis for differentiation between cathepsins L and S

  1999cited by this paper
• Expression of the elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cells.

  1998cited by this paper
• Cysteine proteinases and their endogenous inhibitors: target proteins for prognosis, diagnosis and therapy in cancer (review).

  1998cited by this paper
• Lymph nodes and human tumors (review).

  1998cited by this paper
• Developmental regulation of invariant chain proteolysis controls MHC class II trafficking in mouse dendritic cells.

  1998cited by this paper
• Prognostic values of cathepsin B and carcinoembryonic antigen in sera of patients with colorectal cancer.

  1998cited by this paper
• Crystal structure of human cathepsin S

  1998cited by this paper
• Chemotherapie des nichtkleinzelligen Lungenkarzinoms

  1998cited by this paper
• Graph theory and the entropy concept in histochemistry. Theoretical considerations, application in histopathology and the combination with receptor-specific approaches.

  1997cited by this paper
• Emerging roles for cysteine proteases in human biology.

  1997influential reference
• Enzyme-linked immunosorbent assay for the detection of total cathepsin H in human tissue cytosols and sera.

  1997cited by this paper
• Graph Theory and the EntropyConcept in Histochemistry

  1997cited by this paper
• Folding and activation of human procathepsin S from inclusion bodies produced in Escherichia coli.

  1996cited by this paper
• The lysosomal cysteine protease, cathepsin S, is increased in Alzheimer's disease and Down syndrome brain. An immunocytochemical study.

  1995cited by this paper
• Delivery of nascent MHC class II-invariant chain complexes to lysosomal compartments and proteolysis of invariant chain by cysteine proteases precedes peptide binding in B-lymphoblastoid cells.

  1995cited by this paper
• Assessment of cathepsin L activity by use of the inhibitor CA-074 compared to cathepsin B activity in human lung tumor tissue.

  1995cited by this paper
• CELL AND TISSUE DISTRIBUTION OF LYSOSOMAL CYSTEINE PROTEINASES, CATHEPSINS B, H, AND L, AND THEIR BIOLOGICAL ROLES

  1994cited by this paper
• Engineering the S2 subsite specificity of human cathepsin S to a cathepsin L- and cathepsin B-like specificity.

  1994cited by this paper
• Human cathepsin S: chromosomal localization, gene structure, and tissue distribution.

  1994cited by this paper
• Sequence analysis, tissue distribution, and expression of rat cathepsin S.

  1992cited by this paper
• Primary structure of bovine cathepsin S Comparison to cathepsins L, H, B and papain

  1991cited by this paper
• The specificity of bovine spleen cathepsin S. A comparison with rat liver cathepsins L and B.

  1989influential reference
• Cathepsin S from bovine spleen. Purification, distribution, intracellular localization and action on proteins.

  1989cited by this paper
• CRITLEVEL: An Exploratory Procedure for the Evaluation of Quantitative Prognostic Factors

  1984influential reference
• Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures.

  1981cited by this paper
• Coupling of Enzymes to Antibodies and Antigens

  1978cited by this paper
• Acid sulphydryl protease from calf lymph nodes.

  1975cited by this paper
• The activity of regional nodes in the evolution of immune responses to allogeneic and isogeneic tumors.

  1975cited by this paper
• Nonparametric Estimation from Incomplete Observations

  1958influential reference

• The pH-Dependent Specificity of Cathepsin S and Its Implications for Inflammatory Communications and Disease

  2025cites this paper
• CathepsinDL: Deep Learning-Driven Model for Cathepsin Inhibitor Screening and Drug Target Identification

  2025cites this paper
• Roles of cathepsin S expression levels on the prognosis and tumour microenvironment in clear cell renal cell carcinoma

  2024cites this paper
• Reduced expression of cathepsin F predicts poor prognosis in patients with clear cell renal cell carcinoma

  2024cites this paper
• Cysteine Cathepsins: From Diagnosis to Targeted Therapy of Cancer.

  2024cites this paper
• Advances in Cathepsin S Inhibition: Challenges and Breakthroughs in Drug Development

  2024cites this paper
• Mendelian randomization analyses explore the relationship between cathepsins and lung cancer

  2023cites this paper
• Cysteine Cathepsins as Therapeutic Targets in Immune Regulation and Immune Disorders

  2023cites this paper
• Lysosomal proteases and their role in signaling pathways

  2022cites this paper
• Two SPRi biosensors for the determination of cathepsin S in blood plasma.

  2021cites this paper
• Cathepsin S Evokes PAR2-Dependent Pain in Oral Squamous Cell Carcinoma Patients and Preclinical Mouse Models

  2021cites this paper
• Development and Validation of a Novel Immune-Related Prognostic Model and the Potential Mechanism in Metastatic Synovial Sarcoma

  2021cites this paper
• An Immunosensor for the Determination of Cathepsin S in Blood Plasma by Array SPRi—A Comparison of Analytical Properties of Silver–Gold and Pure Gold Chips

  2021cites this paper
• Ab locks for improving the selectivity and safety of antibody drugs

  2020cites this paper
• The P2X7 purinergic receptor: a potential therapeutic target for lung cancer

  2020cites this paper
• Melatonin attenuates epidermal growth factor‐induced cathepsin S expression in ARPE‐19 cells: Implications for proliferative vitreoretinopathy

  2020cites this paper
• Leading the invasion: The role of Cathepsin S in the tumour microenvironment.

  2020cites this paper
• Application of nanotechnology to target and exploit tumour associated proteases.

  2019cites this paper
• Lysosomal cysteine protease cathepsin S is involved in cancer cell motility by regulating store-operated Ca2+ entry.

  2019cites this paper
• Cigarette smoke induces overexpression of active human cathepsin S in lungs from current smokers with or without COPD.

  2019cites this paper
• Plasma Cathepsin S is Associated with High-density Lipoprotein Cholesterol and Bilirubin in Patients with Abdominal Aortic Aneurysms

  2019cites this paper
• Expression of Proteolytic Enzymes by Small Cell Lung Cancer Circulating Tumor Cell Lines

  2019cites this paper
• Z-FL-COCHO, a cathepsin S inhibitor, enhances oxaliplatin-mediated apoptosis through the induction of endoplasmic reticulum stress

  2018cites this paper
• Regulating BRCA1 protein stability by cathepsin S-mediated ubiquitin degradation

  2018cites this paper
• Cysteine cathepsins as a prospective target for anticancer therapies-current progress and prospects.

  2018cites this paper
• Integrated bioinformatics analysis reveals that the expression of cathepsin S is associated with lymph node metastasis and poor prognosis in papillary thyroid cancer

  2018cites this paper
• Sulforaphane suppresses oral cancer cell migration by regulating cathepsin S expression

  2018cites this paper
• Increased Plasma Cathepsin s at the Time of Percutaneous Transluminal Angioplasty is Associated with 6-months’ Restenosis of the Femoropopliteal Artery

  2018cites this paper
• The transcription factor C/EBP α controls the role of cystatin F during the differentiation of monocytes to macrophages.

  2018cites this paper
• Inhibition of cathepsin S confers sensitivity to methyl protodioscin in oral cancer cells via activation of p38 MAPK/JNK signaling pathways

  2017cites this paper
• Role of Proteases in Tumor Immune Evasion

  2017cites this paper
• Evaluating the diagnostic and prognostic value of circulating cathepsin S in gastric cancer

  2016cites this paper
• Six-SOMAmer Index Relating to Immune, Protease and Angiogenic Functions Predicts Progression in IPF

  2016cites this paper
• Cysteine cathepsin proteases: regulators of cancer progression and therapeutic response

  2015cites this paper
• Lysosomal cysteine peptidases - Molecules signaling tumor cell death and survival.

  2015cites this paper
• Exploring the Molecular Mechanism and Biomakers of Liver Cancer Based on Gene Expression Microarray

  2015cites this paper
• Cathepsin S as a cancer target.

  2015cites this paper
• Involvement of cysteine proteases in cancer.

  2015cites this paper
• Interrelated cathepsin S-lowering and LDL subclass profile improvements induced by atorvastatin in the plasma of stable angina patients.

  2014cites this paper
• Cathepsin S as a biomarker of low-grade inflammation, insulin resistance, and cardiometabolic disease risk

  2014cites this paper
• Cathepsin S as a cancer target Minireview

  2014cites this paper
• Cathepsin S-mediated autophagic flux in tumor-associated macrophages accelerate tumor development by promoting M2 polarization

  2014cites this paper
• miR-31 dysregulation in cystic fibrosis airways contributes to increased pulmonary cathepsin S production.

  2014cites this paper
• Inhibition of cathepsin S induces autophagy and apoptosis in human glioblastoma cell lines through ROS-mediated PI3K/AKT/mTOR/p70S6K and JNK signaling pathways.

  2014cites this paper
• Cysteine cathepsins and their potential in clinical therapy and biomarker discovery

  2014cites this paper
• Impact of the Enhanced Permeability and Retention (EPR) Effect and Cathepsins Levels on the Activity of Polymer-Drug Conjugates

  2014cites this paper
• Cathepsin S from both tumour and tumour-associated cells promote cancer growth

  2013cites this paper
• Cathepsins and Other Proteases in Tumor Angiogenesis

  2013cites this paper
• Synthesis and Radiopharmacological Characterisation of a Fluorine‐18‐Labelled Azadipeptide Nitrile as a Potential PET Tracer for in vivo Imaging of Cysteine Cathepsins

  2013cites this paper
• Cathepsin S from both tumor and tumor‐associated cells promote cancer growth and neovascularization

  2013cites this paper
• Cathepsin S generates soluble CX3CL1 (fractalkine) in vascular smooth muscle cells

  2013cites this paper
• Regulation of cathepsins S and L by cystatin F during maturation of dendritic cells.

  2012cites this paper
• Inhibition of Cathepsin S by Fsn0503 enhances the efficacy of chemotherapy in colorectal carcinomas.

  2012cites this paper
• Silencing cathepsin S gene expression inhibits growth, invasion and angiogenesis of human hepatocellular carcinoma in vitro.

  2012cites this paper
• The Emerging Relevance of the Cysteine Protease Cathepsin S in Disease

  2011cites this paper
• Association between serum cathepsin S and mortality in older adults.

  2011cites this paper
• Expression of cathepsin S and its inhibitor stefin A in sinonasal inverted papilloma.

  2010cites this paper
• Cathepsin S is aberrantly overexpressed in human hepatocellular carcinoma.

  2009cites this paper
• Increased levels of macrophage-secreted cathepsin S during prostate cancer progression in TRAMP mice and patients.

  2009cites this paper
• Proteomics reveals acute pro‐inflammatory and protective responses in rat Kupffer cells and hepatocytes after chemical initiation of liver cancer and after LPS and IL‐6

  2009cites this paper
• Cell-cell interactions in the gastrointestinal tumour-microenvironment

  2009cites this paper
• Molecular Imaging of Proteases in Cancer.

  2009cites this paper
• Levels of Cathepsins S and H in Pleural Fluids of Inflammatory and Neoplastic Origin

  2009cites this paper
• Levels of cathepsins S and H in pleural fluids of inflammatory and neoplastic origin.

  2009cites this paper
• Serum cathepsin K and cystatin C concentration in patients with advanced non-small-cell lung cancer during chemotherapy.

  2009cites this paper
• Vesicle-associated protein 1: a novel ovarian immunocontraceptive target in the common brushtail possum, Trichosurus vulpecula.

  2008cites this paper
• Cysteine Cathepsins and Cystatins as Cancer Biomarkers

  2008cites this paper
• brushtail possum, Trichosurus vulpecula

  2008cites this paper
• IL-18 Is Induced and IL-18 Receptor α Plays a Critical Role in the Pathogenesis of Cigarette Smoke-Induced Pulmonary Emphysema and Inflammation1

  2007influential citation
• Lysosomal Cysteine Proteinase Cathepsin S as a Potential Target for Anti-Cancer Therapy

  2007cites this paper
• Detection of cathepsin S cysteine protease in human brain tumour microdialysates in vivo

  2007cites this paper
• Efficient degradation-aided selection of protease inhibitors by phage display.

  2007cites this paper
• Proteases and their role in chronic inflammatory lung diseases.

  2006cites this paper
• Cystatins in non-small cell lung cancer: tissue levels, localization and relation to prognosis.

  2006cites this paper
• Antiprotease therapy in cancer: hot or not?

  2006cites this paper
• Weight loss reduces adipose tissue cathepsin S and its circulating levels in morbidly obese women.

  2006cites this paper
• Cysteine cathepsins: regulators of antitumour immune response

  2006cites this paper
• Cathepsin S expression: An independent prognostic factor in glioblastoma tumours—a pilot study

  2006influential citation
• Enzyme-targeted fluorescent imaging probes on a multiple antigenic peptide core.

  2006cites this paper
• Role of cathepsins and cystatins in patients with recurrent miscarriage.

  2005cites this paper
• Vegetables affect the expression of genes involved in carcinogenic and anticarcinogenic processes in the lungs of female C57BL/6 mice.

  2005cites this paper
• Inhibitory properties of cystatin F and its localization in U937 promonocyte cells

  2005cites this paper
• Recombinant human procathepsin S is capable of autocatalytic processing at neutral pH in the presence of glycosaminoglycans

  2005cites this paper
• Proteasenexpression einzelner disseminierter Tumorzellen aus Lymphknoten und Knochenmark von Patienten mit nichtkleinzelligem Bronchialkarzinom

  2005cites this paper
• Differentiation‐ and maturation‐dependent content, localization, and secretion of cystatin C in human dendritic cells

  2005cites this paper
• Cathepsin S, a novel biomarker of adiposity: relevance to atherogenesis

  2005cites this paper
• Prognostic Factors in Non-Small Cell Lung Cancer

  2004cites this paper
• Inhibitory p41 isoform of invariant chain and its potential target enzymes cathepsins L and H in distinct populations of macrophages in human lymph nodes

  2004cites this paper
• Cysteine protease cathepsin S as a key step in antigen presentation.

  2004cites this paper
• CD208/dendritic cell-lysosomal associated membrane protein is a marker of normal and transformed type II pneumocytes.

  2004cites this paper
• Cysteine cathepsins in human cancer

  2004cites this paper
• CD 208 / Dendritic Cell-Lysosomal Associated Membrane Protein Is a Marker of Normal and Transformed Type II Pneumocytes

  2004cites this paper
• Cysteine proteases as disease markers.

  2004cites this paper
• Global expression analysis of N-methyl-N'-nitro-N-nitrosoguanidine-induced rat stomach carcinomas using oligonucleotide microarrays.

  2003cites this paper
• Cleavage of Bax to p 18 Bax accelerates stress-induced apoptosis , and a cathepsin-like protease may rapidly degrade p 18 Bax

  2003cites this paper
• Cleavage of Bax to p18 Bax accelerates stress-induced apoptosis, and a cathepsin-like protease may rapidly degrade p18 Bax.

  2003cites this paper
• Gene Expression Versus Sequence for Predicting Function: Glia Maturation Factor Gamma Is Not A Glia Maturation Factor

  2003cites this paper
• Deficiency of the Cysteine Protease Cathepsin S Impairs Microvessel Growth

  2003cites this paper
• The clinical significance of cathepsin S expression in human astrocytomas.

  2003cites this paper
• Lysosomal cathepsins: structure, role in antigen processing and presentation, and cancer.

  2002cites this paper