Abstract
TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) preferentially induces apoptosis of cancer cells without toxicity in normal cells. TRAIL plays an important role in host immune surveillance against tumor metastasis. Cathepsin B (CB) is a mediator of apoptosis whose activity is regulated by its inhibitors, known as cystatins. We examined the TRAIL-mediated cytotoxicity rates of clonally-related primary and metastatic oral cancer (OC) cells and correlated them with the expression levels of TRAIL receptors, cathepsin B and cystatins A, B, C and M. Two pairs of primary (686Tu and 101A) and metastatic (686Ln and 101B) OC cell lines were treated with various concentrations (5 to 1000 ng/ml) of recombinant human TRAIL protein for 14 h, and cell viability and apoptotic rate were determined. In both pairs of cell lines, primary OC cells revealed greater susceptibility to TRAIL than their metastatic counterparts. The protein synthesis inhibitor cycloheximide markedly increased the TRAIL sensitivity of these cell lines, whereas the CB-specific chemical inhibitor CA-074 markedly reduced the sensitivity of primary OC cells to TRAIL. DNA laddering and M30 CytoDEATH immunodetection assays confirmed that TRAIL-induced OC cell death is an apoptotic process. Expression levels of TRAIL death (DR4 and DR5) and decoy (DcR1 and DcR2) receptors were not different between primary and metastatic OC cells. However, expression levels of cystatins were higher in metastatic OC cells than in their respective primary cells, whereas CB levels remain unchanged. Cathepsin B is a mediator of TRAIL-induced apoptosis in OC cells. Elevated levels of cystatins in metastatic OC cells may cause their greater resistance to TRAIL-induced apoptosis. Our data suggest that high expression of cystatins in OC cells may confer a metastatic phenotype by enhancing their resistance to TRAIL.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 103-112 |
| Number of pages | 10 |
| Journal | International Journal of Oncology |
| Volume | 26 |
| Issue number | 1 |
| State | Published - Jan 2005 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Differential susceptibility of metastatic and primary oral cancer cells to TRAIL-induced apoptosis. / Vigneswaran, Nadarajah; Wu, Jean; Nagathihalli, Nagaraj; Adler-Storthz, Karen; Zacharias, Wolfgang.
In: International Journal of Oncology, Vol. 26, No. 1, 01.2005, p. 103-112.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differential susceptibility of metastatic and primary oral cancer cells to TRAIL-induced apoptosis.
AU - Vigneswaran, Nadarajah
AU - Wu, Jean
AU - Nagathihalli, Nagaraj
AU - Adler-Storthz, Karen
AU - Zacharias, Wolfgang
PY - 2005/1
Y1 - 2005/1
N2 - TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) preferentially induces apoptosis of cancer cells without toxicity in normal cells. TRAIL plays an important role in host immune surveillance against tumor metastasis. Cathepsin B (CB) is a mediator of apoptosis whose activity is regulated by its inhibitors, known as cystatins. We examined the TRAIL-mediated cytotoxicity rates of clonally-related primary and metastatic oral cancer (OC) cells and correlated them with the expression levels of TRAIL receptors, cathepsin B and cystatins A, B, C and M. Two pairs of primary (686Tu and 101A) and metastatic (686Ln and 101B) OC cell lines were treated with various concentrations (5 to 1000 ng/ml) of recombinant human TRAIL protein for 14 h, and cell viability and apoptotic rate were determined. In both pairs of cell lines, primary OC cells revealed greater susceptibility to TRAIL than their metastatic counterparts. The protein synthesis inhibitor cycloheximide markedly increased the TRAIL sensitivity of these cell lines, whereas the CB-specific chemical inhibitor CA-074 markedly reduced the sensitivity of primary OC cells to TRAIL. DNA laddering and M30 CytoDEATH immunodetection assays confirmed that TRAIL-induced OC cell death is an apoptotic process. Expression levels of TRAIL death (DR4 and DR5) and decoy (DcR1 and DcR2) receptors were not different between primary and metastatic OC cells. However, expression levels of cystatins were higher in metastatic OC cells than in their respective primary cells, whereas CB levels remain unchanged. Cathepsin B is a mediator of TRAIL-induced apoptosis in OC cells. Elevated levels of cystatins in metastatic OC cells may cause their greater resistance to TRAIL-induced apoptosis. Our data suggest that high expression of cystatins in OC cells may confer a metastatic phenotype by enhancing their resistance to TRAIL.
AB - TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) preferentially induces apoptosis of cancer cells without toxicity in normal cells. TRAIL plays an important role in host immune surveillance against tumor metastasis. Cathepsin B (CB) is a mediator of apoptosis whose activity is regulated by its inhibitors, known as cystatins. We examined the TRAIL-mediated cytotoxicity rates of clonally-related primary and metastatic oral cancer (OC) cells and correlated them with the expression levels of TRAIL receptors, cathepsin B and cystatins A, B, C and M. Two pairs of primary (686Tu and 101A) and metastatic (686Ln and 101B) OC cell lines were treated with various concentrations (5 to 1000 ng/ml) of recombinant human TRAIL protein for 14 h, and cell viability and apoptotic rate were determined. In both pairs of cell lines, primary OC cells revealed greater susceptibility to TRAIL than their metastatic counterparts. The protein synthesis inhibitor cycloheximide markedly increased the TRAIL sensitivity of these cell lines, whereas the CB-specific chemical inhibitor CA-074 markedly reduced the sensitivity of primary OC cells to TRAIL. DNA laddering and M30 CytoDEATH immunodetection assays confirmed that TRAIL-induced OC cell death is an apoptotic process. Expression levels of TRAIL death (DR4 and DR5) and decoy (DcR1 and DcR2) receptors were not different between primary and metastatic OC cells. However, expression levels of cystatins were higher in metastatic OC cells than in their respective primary cells, whereas CB levels remain unchanged. Cathepsin B is a mediator of TRAIL-induced apoptosis in OC cells. Elevated levels of cystatins in metastatic OC cells may cause their greater resistance to TRAIL-induced apoptosis. Our data suggest that high expression of cystatins in OC cells may confer a metastatic phenotype by enhancing their resistance to TRAIL.
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UR - http://www.scopus.com/inward/citedby.url?scp=13644253361&partnerID=8YFLogxK
M3 - Article
C2 - 15586230
AN - SCOPUS:13644253361
VL - 26
SP - 103
EP - 112
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 1
ER -