Differential susceptibility of metastatic and primary oral cancer cells to TRAIL-induced apoptosis.

Nadarajah Vigneswaran, Jean Wu, Nagaraj Nagathihalli, Karen Adler-Storthz, Wolfgang Zacharias

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)103-112
Number of pages10
JournalInternational Journal of Oncology
Volume26
Issue number1
StatePublished - Jan 2005
Externally publishedYes

Fingerprint

Mouth Neoplasms
Apoptosis
Cathepsin B
Cystatins
Cell Line
Receptors, Tumor Necrosis Factor, Member 10c
Cystatin M
Cystatin B
Cystatin A
TNF-Related Apoptosis-Inducing Ligand Receptors
Protein Synthesis Inhibitors
Cycloheximide
Neoplasms
Cell Survival
Cell Death
Tumor Necrosis Factor-alpha
Neoplasm Metastasis
Ligands
Phenotype

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 journalArticle

Vigneswaran, Nadarajah ; Wu, Jean ; Nagathihalli, Nagaraj ; Adler-Storthz, Karen ; Zacharias, Wolfgang. / Differential susceptibility of metastatic and primary oral cancer cells to TRAIL-induced apoptosis. In: International Journal of Oncology. 2005 ; Vol. 26, No. 1. pp. 103-112.
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