A comparative study of Fas and Fas-ligand expression during melanoma progression

Soubrane, Claude; Mouawad, Roger; Antoine, E.; Vérola, O; Gil-Delgado, M.; Khayat, David

doi:10.1046/j.1365-2133.2000.03655.x

Cited by 55 publications

(46 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In accordance with our findings, recent flowcytometric analysis has revealed that Fas-positive melanoma cells decreased as primary melanoma thickness progressively increased (32). In addition, it has been reported that the increased soluble Fas level correlates with poor prognosis in advanced melanomas (33,34) and that the soluble FasL levels in melanoma patients are higher than those in healthy donors (34).…”

Section: Discussionsupporting

confidence: 92%

Fas-Mediated Apoptosis of Melanoma Cells and Infiltrating Lymphocytes in Human Malignant Melanomas

2002

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 92%

Fas-Mediated Apoptosis of Melanoma Cells and Infiltrating Lymphocytes in Human Malignant Melanomas

2002

View full text Add to dashboard Cite

“…These results are also convergent with the results of other authors that human and mouse melanoma cells express Fas ligand but hardly any Fas, which may contribute to their immune privilege [3,34]. Similar results were presented by Soubrane et al [28], who determinated the expression of Fas and its ligand (FasL) on normal skin cells (mixture of keratinocytes and melanocytes), and primary and metastatic melanoma cells from patients, using monoclonal antibodies and flow cytometric analysis of labelled cells. They found that Fas expression was significantly higher on normal control skin cells than on cells from tumours, whatever the stage studied.…”

Section: Discussionsupporting

confidence: 80%

“…Different types of tumour cells have been shown to escape immune recognition by constitutive resistance to Fas-mediated apoptosis [6,7,25]. Melanoma cells are often characterized by reduced Fas expression and/or death signalling function, rendering them resistant to cell death mediated by FasL [3,17,27,28,29]. Due to a higher FasL expression, tumour cells can induce apoptosis of immune cells [7,17].…”

Section: Discussionmentioning

confidence: 99%

Fas and FasL expression on cells of two transplantable melanoma lines according to their different biological properties.

Zielińska

Kozłowska²,

Cichorek³

et al. 2008

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

Abstract. Fas and FasL interaction induces apoptotic cell death. In immunocompetent cells it plays a crucial role in the effector functions of the cells and in the regulation of host immune response. In tumours (e.g. melanoma), FasL expression possibly counteracts the Fas-positive effector T cells that infiltrate into tumours, and consequently the Fas/FasL interaction can contribute to the escape of tumour cells from the systemic immune response. In this study we examined differences in Fas and FasL expression on cells from the hamster melanotic melanoma line (Ma) and a more aggressive amelanotic melanoma line (Ab). We also tried to find out whether the Fas/FasL expression induces an ability to undergo spontaneous apoptosis in these two transplantable melanoma lines. Our previous studies have shown that cells of the Ma line have a higher ability to undergo spontaneous apoptosis than cells of the Ab line. Isolated transplantable melanoma cells were incubated for 4 and 24 hours and after that time the expression of Fas and FasL was estimated by flow cytometry. The results show that there was no Fas expression, although FasL was detected on both melanoma cell lines. Therefore the data reported by other authors indicate that a lack or a low level of Fas expression and an ectopic expression of FasL on melanoma cells can be an escape mechanism of the tumour, to avoid host immune responses. The content of FasL-positive melanotic melanoma cells was higher than in amelanotic melanoma cells and increased with the prolongation of the incubation time. FasL expression on amelanotic melanoma cells was detected after 24 hours at a level similar to that on melanotic melanoma cells after 4 hours incubation time. FasL expression on melanoma cells can induce apoptosis in cytotoxic T lymphocytes and NK cells which are responsible for tumour cells elimination. The results obtained suggest that the Fas/FasL system does not play any significant role in spontaneous apoptosis of two melanoma cell lines. But these results may indicate the presence of immune privilege of tumour cells with FasL expression.

show abstract

“…In this study, we have shown that Mcl-1 protein, a member of the Bcl-2 antiapoptotic family, plays a major role in the resistance of melanoma cells toward Fas-mediated apoptosis. Several studies have shown that melanoma tumor cells express variable levels of Fas in vivo and in vitro but were found to be resistant to Fasinduced apoptosis (35,36), suggesting that additional mechanisms at the level of Fas-induced caspase activation are likely to contribute to the observed resistance. We show that Mcl-1 is constitutively expressed in resistant melanoma cell lines and its knockdown using siRNA sensitizes these cells toward Fasinduced apoptosis, whereas overexpression of Mcl-1 protects sensitive melanoma cell lines from Fas-induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Down-Regulation of Mcl-1 by Small Interfering RNA Sensitizes Resistant Melanoma Cells to Fas-Mediated Apoptosis

Chetoui

Sylla

Gagnon-Houde

et al. 2008

Molecular Cancer Research

View full text Add to dashboard Cite

Resistance of malignant melanoma cells to Fas-mediated apoptosis is among the mechanisms by which they escape immune surveillance. However, the mechanisms contributing to their resistance are not completely understood, and it is still unclear whether antiapoptotic Bcl-2 -related family proteins play a role in this resistance. In this study, we report that treatment of Fas-resistant melanoma cell lines with cycloheximide, a general inhibitor of de novo protein synthesis, sensitizes them to anti-Fas monoclonal antibody (mAb) -induced apoptosis. The cycloheximide-induced sensitization to Fas-induced apoptosis is associated with a rapid down-regulation of Mcl-1 protein levels, but not that of Bcl-2 or Bcl-xL. Targeting Mcl-1 in these melanoma cell lines with specific small interfering RNA was sufficient to sensitize them to both anti-Fas mAb-induced apoptosis and activation of caspase-9.

show abstract

A comparative study of Fas and Fas-ligand expression during melanoma progression

Abstract: These results suggest that downregulation of CD95 and upregulation of Fas-L in melanoma might be considered as concomitant with disease progression.

Cited by 55 publications

References 13 publications

Fas-Mediated Apoptosis of Melanoma Cells and Infiltrating Lymphocytes in Human Malignant Melanomas

Fas-Mediated Apoptosis of Melanoma Cells and Infiltrating Lymphocytes in Human Malignant Melanomas

Fas and FasL expression on cells of two transplantable melanoma lines according to their different biological properties.

Down-Regulation of Mcl-1 by Small Interfering RNA Sensitizes Resistant Melanoma Cells to Fas-Mediated Apoptosis

Contact Info

Product

Resources

About