Soluble Fas (<i>sFas</i>) and soluble Fas ligand (<i>sFas‐L</i>) balance in laryngeal carcinoma before and after surgical treatment

Arisi, E.; Sambataro, G.; Corsi, Massimiliano M.

doi:10.1002/jso.10246

Cited by 10 publications

(11 citation statements)

References 33 publications

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“…[1][2][3]5,7,12 It was also confirmed in several studies that surgical removal of tumors reduced sFas levels. 4,13,14 As Holdenrieder and Stieber described in their review, 15 cancer itself has some self-defense mechanisms for avoiding apoptosis, one of which must be sFas.…”

Section: Discussionmentioning

confidence: 99%

Soluble Fas level and cancer mortality: Findings from a nested case–control study within a large‐scale prospective study

Tamakoshi¹,

Nakachi²,

Ito³

et al. 2008

Intl Journal of Cancer

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Soluble Fas (sFas) is known to play an important role in the development of cancers of various sites. To confirm whether or not the serum sFas level can be a predictor of cancer, we conducted a nested case-control study within a large-scale population-based cohort study in Japan. Serum samples were collected from 39,242 participants (13,839 men and 25,403 women) at baseline, all of whom were followed until 1997 for mortality and until 1994 for cancer incidence. Three controls were randomly selected and matched to each cancer case for gender, age and residential area. Serum values of sFas were measured by enzyme-linked immuno-adsorbent assay, using commercially available kits. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using conditional logistic models, based on 798 total cancer mortality cases and their 2,353 matched controls. The risk of total cancer mortality was increased according to sFas levels, and the OR of the highest quartile compared with that of the lowest was 1.81 (95% CI; 1.40-2.34) after adjusting for smoking and drinking status, and body mass index. This positive association remained unaltered when cases were divided into 2 groups according to the observation period. Our results suggest that serum sFas has a possibility to detect people at high risk for cancer prior to diagnosis, since it increased before cancer diagnosis in those apparently healthy people. ' 2008 Wiley-Liss, Inc.Key words: soluble Fas; cancer; cohort study; nested case-control study Fas on membrane of many cells induces cell apoptosis by binding to the Fas ligand that is expressed predominantly in activated T cells. This interaction between Fas and Fas ligand is known to play an important role in the spontaneous death of cancer cells induced by the immune system. Another form of Fas, circulating soluble Fas (sFas), antagonizes the cell-surface Fas function and may offer a survival advantage to cells. Previous studies have demonstrated that sFas levels were increased in cancer patients from many sites.1-5 Furthermore, the overexpression of sFas in serum is correlated with a cancer stage and/or prognosis. 1,6,7 Given that much of the evidence is derived from case-control studies, it is plausible that an elevation of the sFas level in serum might contribute to a tumor escaping from Fas-induced apoptosis. However, it remains unclear whether individuals with high sFas levels are at an increased risk of cancer, i.e., whether or not sFas levels can predict cancer occurrence. Only 1 paper 8 has examined the relationship between sFas levels and ovarian cancer in a nested case-control study. The authors failed to find any association between serum sFas levels and ovarian cancer occurrences, which were diagnosed at an average of 5.1 years after blood was drawn. To test the hypothesis that elevated serum sFas could be a predictive marker of cancer and to identify people at risk of cancer, we examined the relationship between serum sFas levels and the risk of cancer mortality in a nested case-control study wi...

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Section: Discussionmentioning

confidence: 99%

Soluble Fas level and cancer mortality: Findings from a nested case–control study within a large‐scale prospective study

Tamakoshi¹,

Nakachi²,

Ito³

et al. 2008

Intl Journal of Cancer

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“…sFas is one of the alternatively spliced variants of Fas which does not have the transmembrane domain and thus is readily secreted [Cheng et al, 1994]. Serum levels of sFas are reported to be higher in cancer patients, including those with SCCHN, than in healthy controls [Knipping et al, 1995;Alecu et al, 2002;Furuya et al, 2003;Pignataro et al, 2003]. Although sFas was detected in culture supernatants of SCCHN cells, its levels did not correlate with the susceptibility of these cells to Fas-induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

FAP‐1‐mediated activation of NF‐κB induces resistance of head and neck cancer to fas‐induced apoptosis

Wieckowski

Atarashi

Stanson

et al. 2006

J of Cellular Biochemistry

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Molecular mechanisms responsible for tumor resistance to apoptosis often involve the Fas/FasL pathway. While squamous cell carcinomas of the head and neck (SCCHN) express both Fas and FasL, their resistance to self-induced apoptosis or apoptosis mediated by Fas agonistic antibody (CH-11Ab) was independent of the level of Fas surface expression or the presence of soluble Fas in supernatants of primary or metastatic SCCHN cell lines. By in vitro immunoselection, using PCI-15A cell line treated with successive cycles of CH-11 Ab, Fas-resistant sublines with the parental genotype were selected. Such sublines failed to cleave caspase-8 upon Fas engagement and were resistant to CH-11 Ab, although they remained sensitive to VP-16 or staurosporin. In the presence of cycloheximide, the selected SCCHN sublines become susceptible to CH-11 Ab, and showed cleavage of caspase-8, suggesting that apoptosis resistance was mediated by an inhibitory protein(s) acting upstream of caspase-8. Overexpression of Fas-associated phosphatase 1 (FAP-1), but not cellular FLICE-inhibitory protein (cFLIP) in SCCHN sublines was documented by Western blots and RT-PCR analyses. The FAP-1 þ selected sublines also downregulated cell surface Fas. A high phosphorylation level of IkBk, NFkB activation and upregulation of Bcl-2 expression were observed in the FAP-1 þ sublines. Treatment with the phosphatase inhibitor, orthovanadate, or silencing of FAP-1 with siRNA abolished their resistance to apoptosis, suggesting that FAP-1 phosphatase activity could be responsible for NF-kB activation and resistance of SCCHN cells to Fas-mediated apoptosis.

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“…15 Also Pignataro et al 9 found that the loss of Fas receptors is a common feature of most human malignancies and are associated with the progression of cancers, including SCCHN. Therefore, the variants of the Fas could be expected to have an effect on cell death, and thus, carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…8 Fas and its specific ligand (Fas-L), both of which are involved in apoptosis, exist in membranebound and soluble forms(sFas). 9 Because of the role of the Fas genes in regulating cell death, and because abnormal expression of Fas have been observed in a variety of tumors, including SCCHN, we assess serum sFas levels in patients with different stages of laryngeal squamous cell carcinoma (LSCC) according to TNM classification to investigate its prognostic significance, we also correlate its level with the host immune response via the ultrastructural study of the buffy coat.…”

Section: Introductionmentioning

confidence: 99%

The Role of sFas in the Immune Escape Mechanism and Progression of Cancer Larynx

Badry

Elmofty

Helmy

2009

Clinical medicine. Ear, nose and throat

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This work assess serum levels of soluble Fas form (sFas) in patients with different stages of laryngeal squamous cell carcinoma(LSCC) to investigate its prognostic significance. We correlate its levels with the morphological changes of peripheral blood cells via buffy coat examinatin. The study population included 70 patients clinically diagnosed and pathohistologically confirmed LSCC in addition to 20 healthy controls. According to TNM classification 33(47.1%) patients were in stage I (group I) and 24(34.3%) in stage II (group II) , 13(18.5%) in stage III (group III). The results revealed that the mean serum level of sFas (pg/ml) in the control group was 51.2, in group I was 66.33, in group II was 81.33 and in group III was 112.45. Statistical analysis of the mean of sFas by ELISA test in the patients' groups in comparison to the control revealed a significant increase of both group II and III in comparison to the control group (P  0.01) but there was no significant difference (P  0.05) between group I in comparison to either the control or group II. There was a significant difference (P  0.05) between group I in comparison to group III. LM examination revealed massive extent of the apoptotic cells in group III when compared to both group I and group II. EM examination of the buffy coat revealed apoptotic changes, mainly in the peripheral blood mononuclear cells (PBMNCs), represented by surface membrane ruffles and blebs with clumped nuclear chromatin and vacuolated cytoplasm. In conclusion, this study may help us to better understand one of the escape mechanisms in cancer larynx. This mechanism is represented by the significant increase in both the serum level of sFas and the morphological apoptotic changes that detected in PBMNCs. Soluble Fas may contribute to the progression of laryngeal cancer. It can be used as an attractive target for anticancer therapy and may be considered as a marker of disease progression and poor prognosis in laryngeal cancer.

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Soluble Fas (sFas) and soluble Fas ligand (sFas‐L) balance in laryngeal carcinoma before and after surgical treatment

Abstract: The decrease in sFas and sFas-L levels after surgery suggest that they may be produced by or closely linked to tumour cells. Larger prospective clinical studies of patients with LSCC will be needed to establish the clinical significance of sFas and sFas-L, as reported for other neoplasms.

Cited by 10 publications

References 33 publications

Soluble Fas level and cancer mortality: Findings from a nested case–control study within a large‐scale prospective study

Soluble Fas level and cancer mortality: Findings from a nested case–control study within a large‐scale prospective study

FAP‐1‐mediated activation of NF‐κB induces resistance of head and neck cancer to fas‐induced apoptosis

The Role of sFas in the Immune Escape Mechanism and Progression of Cancer Larynx

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