Hypoxia alters cathepsin B / inhibitor profiles in oral carcinoma cell lines.

Wickramasinghe NS, Banerjee K, Nagaraj NS, Vigneswaran N, Zacharias W
Anticancer Res. 2005 25 (4): 2841-9

PMID: 16080536

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.

MeSH Terms (15)

Aged Carcinoma, Squamous Cell Cathepsin B Cell Growth Processes Cell Hypoxia Cell Line, Tumor Cystatin B Cystatin C Cystatins Cysteine Proteinase Inhibitors Humans Hypopharyngeal Neoplasms Male Middle Aged Mouth Neoplasms

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