Hypoxia Alters Cathepsin B / Inhibitor Profiles in Oral Carcinoma Cell Lines

Background: The tumor microenvironment is believed to contribute to the malignant properties of tumor cells in heterogeneous tumor tissues. We investigated the impact of hypoxia (1% oxygen) on the expression of cathepsin B and its natural inhibitors cystatin B and C. Materials and Methods: Patient-m...

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Veröffentlicht in:Anticancer research 2005-07, Vol.25 (4), p.2841-2849
Hauptverfasser: WICKRAMASINGHE, Nalinie S, BANERJEE, Kasturi, NAGARAJ, Nagathihalli S, VIGNESWARAN, Nadarajah, ZACHARIAS, Wolfgang
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container_issue 4
container_start_page 2841
container_title Anticancer research
container_volume 25
creator WICKRAMASINGHE, Nalinie S
BANERJEE, Kasturi
NAGARAJ, Nagathihalli S
VIGNESWARAN, Nadarajah
ZACHARIAS, Wolfgang
description Background: The tumor microenvironment is believed to contribute to the malignant properties of tumor cells in heterogeneous tumor tissues. We investigated the impact of hypoxia (1% oxygen) on the expression of cathepsin B and its natural inhibitors cystatin B and C. Materials and Methods: Patient-matched oral carcinoma cell lines from primary tumor and lymph node metastasis were used to study the effects of hypoxia on proliferation, protein expression, and proteolytic and inhibitor activities. Results: Hypoxic growth led to elevated cathepsin B expression and activity, and this effect was greater in metastatic than in primary tumor cells. Also, hypoxia led to down-regulation of the inhibitors cystatin C and B, resulting in increased residual activity of cathepsin B. Conclusion: These data suggest that the invasive and/or metastatic potential of cells may be enhanced under hypoxia by increasing cathepsin-mediated proteolysis. The results provide strong evidence for the involvement of cathepsin B and its cystatin inhibitors in hypoxia-enhanced tumor progression.
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We investigated the impact of hypoxia (1% oxygen) on the expression of cathepsin B and its natural inhibitors cystatin B and C. Materials and Methods: Patient-matched oral carcinoma cell lines from primary tumor and lymph node metastasis were used to study the effects of hypoxia on proliferation, protein expression, and proteolytic and inhibitor activities. Results: Hypoxic growth led to elevated cathepsin B expression and activity, and this effect was greater in metastatic than in primary tumor cells. Also, hypoxia led to down-regulation of the inhibitors cystatin C and B, resulting in increased residual activity of cathepsin B. Conclusion: These data suggest that the invasive and/or metastatic potential of cells may be enhanced under hypoxia by increasing cathepsin-mediated proteolysis. The results provide strong evidence for the involvement of cathepsin B and its cystatin inhibitors in hypoxia-enhanced tumor progression.</description><identifier>ISSN: 0250-7005</identifier><identifier>EISSN: 1791-7530</identifier><identifier>PMID: 16080536</identifier><language>eng</language><publisher>Attiki: International Institute of Anticancer Research</publisher><subject>Aged ; Biological and medical sciences ; Carcinoma, Squamous Cell - enzymology ; Carcinoma, Squamous Cell - pathology ; Cathepsin B - antagonists &amp; inhibitors ; Cathepsin B - metabolism ; Cell Growth Processes - physiology ; Cell Hypoxia - physiology ; Cell Line, Tumor ; Cystatin B ; Cystatin C ; Cystatins - metabolism ; Cysteine Proteinase Inhibitors - metabolism ; Humans ; Hypopharyngeal Neoplasms - enzymology ; Hypopharyngeal Neoplasms - pathology ; Male ; Medical sciences ; Middle Aged ; Mouth Neoplasms - enzymology ; Mouth Neoplasms - pathology ; Otorhinolaryngology. 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We investigated the impact of hypoxia (1% oxygen) on the expression of cathepsin B and its natural inhibitors cystatin B and C. Materials and Methods: Patient-matched oral carcinoma cell lines from primary tumor and lymph node metastasis were used to study the effects of hypoxia on proliferation, protein expression, and proteolytic and inhibitor activities. Results: Hypoxic growth led to elevated cathepsin B expression and activity, and this effect was greater in metastatic than in primary tumor cells. Also, hypoxia led to down-regulation of the inhibitors cystatin C and B, resulting in increased residual activity of cathepsin B. Conclusion: These data suggest that the invasive and/or metastatic potential of cells may be enhanced under hypoxia by increasing cathepsin-mediated proteolysis. 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subjects Aged
Biological and medical sciences
Carcinoma, Squamous Cell - enzymology
Carcinoma, Squamous Cell - pathology
Cathepsin B - antagonists & inhibitors
Cathepsin B - metabolism
Cell Growth Processes - physiology
Cell Hypoxia - physiology
Cell Line, Tumor
Cystatin B
Cystatin C
Cystatins - metabolism
Cysteine Proteinase Inhibitors - metabolism
Humans
Hypopharyngeal Neoplasms - enzymology
Hypopharyngeal Neoplasms - pathology
Male
Medical sciences
Middle Aged
Mouth Neoplasms - enzymology
Mouth Neoplasms - pathology
Otorhinolaryngology. Stomatology
Tumors
Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology
title Hypoxia Alters Cathepsin B / Inhibitor Profiles in Oral Carcinoma Cell Lines
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