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

Shukuwa, Tetsuo; Katayama, Ichiro; Koji, Takehiko

doi:10.1038/modpathol.3880535

Cited by 19 publications

(21 citation statements)

References 31 publications

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“…Many inducers and inhibitors of this way of apoptosis have been reported. It is well recognized that the Fas/FasL pathway is involved in the apoptotic process in different pathologies and in the cytotoxic effects of most immuno-and chemotherapeutic agents [1,2,26,27]. The expression and function of the Fas receptor play an important role in the maintaining of homeostasis.…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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.

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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.

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Section: Discussionmentioning

confidence: 99%

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.

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“…Apoptosis of TIL may cause depletion of lymphocytes and negatively affects prognosis. Apoptotic signals directed against lymphocytes have been studied extensively in FasFasL system (23)(24)(25). FasL is expressed in the stroma of the eye and Sertoli cells of the testis and is known to induce apoptosis of infiltrating lymphocytes (5,8).…”

Section: Discussionmentioning

confidence: 99%

Expression of Tumor-Associated Membrane Antigen, RCAS1, in Human Colorectal Carcinomas and Possible Role in Apoptosis of Tumor-Infiltrating Lymphocytes

Okada

Nakashima²,

Komuta

et al. 2003

Modern Pathology

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RCAS1, a novel tumor-associated antigen, is expressed in advanced human neoplasias including uterine and ovarian carcinomas. RCAS1 protein was indicated to induce cell cycle arrest and apoptosis of cultured human lymphoid and myeloid cell lines and normal lymphocytes. In the present study, we investigated the expression and prognostic value of RCAS1 in 58 patients with colorectal carcinomas. RCAS1 protein was detected by immunoperoxidase staining using a mouse monoclonal anti-RCAS1 antibody (22-1-1 antibody). Immunohistochemical examination showed expression of RCAS1 in 75% of colorectal carcinomas with lymph node metastases (n ‫؍‬ 24), whereas it was present in only 41% of tumors without metastases (n ‫؍‬ 34, P < .05). Patients with RCAS1-positive tumors showed a significantly poorer prognosis than those negative for RCAS1 (P < .05). Multivariate analysis using the Cox regression model indicated that RCAS1 positivity was an independent negative predictor for survival (P ‫؍‬ .0300; risk ratio, 0.496). In addition, apoptotic cells of tumor-infiltrating lymphocytes were examined using nonradioactive in situ nick translation in paraffin-embedded sections. The proportion of apoptotic tumor-infiltrating lymphocytes was significantly higher in RCAS1-positive colorectal carcinomas (11.2 ؎ 1.0) than in RCAS1-negative tumors (7.9 ؎ 1.0, P < .05). Our results suggest that overexpression of RCAS1 may negatively affect the prognosis of human colorectal carcinomas and that RCAS1 may play a role in tumor immune privilege in vivo.

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“…29,30 Anti-FasL (1: 200; P5) was generated with a synthetic peptide corresponding to the intracellular domain (P5; amino acids 41-55) of rat FasL. 31,32 Anti-CD8 (1: 100) was purchased from MBL (Nagoya, Japan). Horseradish peroxidase (HRP)-labeled goat anti-mouse IgG (1: 100) and HRP-labeled goat anti-rabbit IgG (1: 200) were purchased from MBL.…”

Section: Antibodiesmentioning

confidence: 99%

Possible correlation between iron deposition and enhanced proliferating activity in hepatitis C virus-positive hepatocellular carcinoma in Myanmar (Burma)

et al. 2007

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

Cited by 19 publications

References 31 publications

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

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

Expression of Tumor-Associated Membrane Antigen, RCAS1, in Human Colorectal Carcinomas and Possible Role in Apoptosis of Tumor-Infiltrating Lymphocytes

Possible correlation between iron deposition and enhanced proliferating activity in hepatitis C virus-positive hepatocellular carcinoma in Myanmar (Burma)

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