Apoptotic Inhibition of Head and Neck Squamous Cell Carcinoma Cells by Tumor Necrosis Factor

Briskin, Kenneth B.; Fady, Catherine; Wang, Marilene; Lichtenstein, Alan

doi:10.1001/archotol.1996.01890170091016

Cited by 7 publications

(7 citation statements)

References 15 publications

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“…In the present study, we confirmed that the 3 human UM-SCC cell lines previously shown to exhibit constitutive activation of NF-κB are highly resistant to TNF-α induced cell death. Our results which demonstrate a relatively high resistance of these 3 UM-SCC cell lines to TNF-α cytotoxicity are consistent with several studies with different panels of cell lines, which showed that resistance of HNSCC to TNF-α is common (Gapany et al, 1990, Schuger et al, 1990, Sacchi et al, 1991, Monchimatsu et al, 1993, Briskin et al, 1996. The UM-SCC cell lines in the present study exhibited limited sensitivity at 10 4 U/ml TNF-α, consistent with results obtained in another laboratory with a different panel of HNSCC cell lines (Briskin et al, 1996).…”

Section: supporting

confidence: 92%

“…TNF-α has been shown to induce cell death of tumours via apoptosis or necrosis (Schmid et al, 1986;Dealtry et al, 1987;Larrick and Wright, 1990;Laster et al, 1998). TNF-α can induce apoptosis of some HNSCC cell lines at concentrations at or above 10 4 U/ml (Briskin et al, 1996), but most human HNSCC have been reported to be relatively resistant to TNF-α (Gapany et al, 1990, Schuger et al, 1990Sacchi et al, 1991, Monchimatsu et al, 1993, Briskin et al, 1996. Development of resistance to TNF-α has been shown to occur with tumour progression in murine fibrosarcomas through exposure of tumour cells to TNF-α produced by host responses, and selection of TNF-α resistant tumour cells (Urban et al, 1983(Urban et al, , 1986).…”

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confidence: 99%

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Inhibition of transcription factor nuclear factor-κB by a mutant inhibitor-κBα attenuates resistance of human head and neck squamous cell carcinoma to TNF-α caspase-mediated cell death

et al. 2000

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Tumour necrosis factor-α (TNF-α) is a cytokine that can induce cell death of different cancers via a cellular cascade of proteases, the caspases. However, TNF-α has been detected in tumour and serum of patients with head and neck squamous cell carcinoma (HNSCC), and tumour cell lines derived from this environment often exhibit resistance to TNF-α-induced cell death. Cell death mediated by TNF-α and caspases may be inhibited by cytoprotective genes regulated by transcription factor nuclear factor-κB (NF-κB). We recently showed that NF-κB is constitutively activated in HNSCC, and that inhibition of NF-κB by expression of a nondegradable mutant inhibitor of NF-κB, IκBαM, markedly decreased survival and growth of HNSCC cells in vivo. In the present study, we examined the TNF-α sensitivity and response of HNSCC with constitutively active NF-κB, and of HNSCC cells in which NF-κB is inhibited by stable expression of a dominant negative mutant inhibitor, IκBαM. Human lines UM-SCC-9, 11B and 38, previously shown to exhibit constitutive activation of NF-κB, were found to be highly resistant to growth inhibition by up to 104U/ml of TNF-α in 5 day MTT assay. These TNF-α resistant HNSCC lines expressed TNF receptor I, and exhibited constitutive and TNF-α-inducible activation of NF-κB as demonstrated by nuclear localization of NF-κB p65 by immunohistochemistry. UM-SCC-9 I11 cells which stably expressed an inhibitor of NF-κB, IκBαm, were susceptible to TNF-α-induced growth inhibition. DNA cell cycle analysis revealed that TNF-α induced growth inhibition was associated with accumulation of cells with sub-G0/G1 DNA content. Cell death was demonstrated by trypan blue staining, and was blocked by caspase inhibitor. We conclude that HNSCC that exhibit constitutive and TNF-α-inducible activation of transcription factor NF-κB are resistant to TNF-α, and that inhibition of NF-κB sensitizes HNSCC to TNF-α caspase-mediated cytotoxicity. The demonstration of the role of activation of NF-κB in resistance of HNSCC to TNF-α may be helpful in the identification of potential targets for pharmacological, molecular and immune therapy of HNSCC. © 2000 Cancer Research Campaign

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Section: supporting

confidence: 92%

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confidence: 99%

Inhibition of transcription factor nuclear factor-κB by a mutant inhibitor-κBα attenuates resistance of human head and neck squamous cell carcinoma to TNF-α caspase-mediated cell death

et al. 2000

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“…In addition, patients with lung adenocarcinoma had decreased numbers of peripheral blood TNF-alpha-producing monocytes upon LPS stimulation [61]. The mechanisms of TNF-alpha suppression in the circumstances mentioned are not known, but these observations are not surprising, as TNF-alpha toxicity necessitates its tight control during immune responses to microbial insults.…”

Section: Discussionmentioning

confidence: 99%

Squamous Carcinoma Cells Influence Monocyte Phenotype and Suppress Lipopolysaccharide-Induced TNF-alpha in Monocytes

et al. 2010

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Bacteria and chronic inflammation are present in squamous cell carcinoma of the head and neck (HNSCC), but their roles in the pathogenesis of HNSCC are unclear. Our studies described here revealed that human monocytes co-cultured short term with HNSCC cells were more likely to express CD16, and CD16+ small mononuclear cells were common in HNSCC specimens. In addition, we identified monocytes as the primary source of LPS-induced IL-6 and TNF-alpha in the monocyte-HNSCC co-cultures. Remarkably, relative to LPS-stimulated monocytes cultured alone, HNSCC cells profoundly suppressed LPS-induced TNF-alpha in monocytes, without compromising IL-6 production. High levels of cytoprotective factors like IL-6 and low levels of TNF-alpha are important for the tumor microenvironment that enables tumor cell survival, affects monocyte differentiation and may contribute to tumor colonization by bacteria. This study provides novel observations that HNSCC cells affect monocyte phenotype and function, which are relevant to the regulation of the HNSCC microenvironment.

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“…The functional implications of the soluble forms of members of the TNF receptor family have not been fully explored.The cytoplasmic domains of most members of the TNF receptor family are different from each other, some transduce cell death, whereas others promote growth(83). TNFRI and Fas have been shown to transduce apoptotic signals in cells(84,85), including OSCC cells(86,87). The cytoplasmic domains of some members of the TNF receptor family bear 'death domain' motifs required for apoptosis(54,88).…”

mentioning

confidence: 99%

Cell death regulation in oral squamous cell carcinoma: methodological considerations and clinical significance

Loro¹,

Vintermyr

Johannessen³

2003

J Oral Pathology Medicine

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In the last three decades, more work has been done on apoptosis and its role in the pathogenesis of many diseases including cancer. In almost all instances of cancer, dysregulation of cell death (apoptosis) and cell proliferation have been found to play a major role in tumourigenesis. A lot of progress has been made on understanding the molecular basis of apoptosis and its regulatory mechanisms. This review focuses on current knowledge on the regulation of apoptosis in oral squamous cell carcinoma, current methodologies and methodological consideration in estimation of cell death in tissue sections and the clinical significance of apoptosis related molecules in progression of oral squamous cell carcinoma.

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Apoptotic Inhibition of Head and Neck Squamous Cell Carcinoma Cells by Tumor Necrosis Factor

Cited by 7 publications

References 15 publications

Inhibition of transcription factor nuclear factor-κB by a mutant inhibitor-κBα attenuates resistance of human head and neck squamous cell carcinoma to TNF-α caspase-mediated cell death

Inhibition of transcription factor nuclear factor-κB by a mutant inhibitor-κBα attenuates resistance of human head and neck squamous cell carcinoma to TNF-α caspase-mediated cell death

Squamous Carcinoma Cells Influence Monocyte Phenotype and Suppress Lipopolysaccharide-Induced TNF-alpha in Monocytes

Cell death regulation in oral squamous cell carcinoma: methodological considerations and clinical significance

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