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.


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.


CONCLUSIONS
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.
Wickramasinghe
Nalinie S
NS
Department of Medicine, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202, USA.
Banerjee
Kasturi
K
Nagaraj
Nagathihalli S
NS
Vigneswaran
Nadarajah
N
Zacharias
Wolfgang
W
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048708:Cell Growth Processes / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D055313:Cystatin B; D055316:Cystatin C; D015891:Cystatins / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism*; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000473:pathology
C525030:CST3 protein, human; C524994:CSTB protein, human; D055316:Cystatin C; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; D055313:Cystatin B; D002401:Cathepsin B