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

Abstract

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.

Effects of FasL Expression in Oral Squamous Cell Cancer

“…As shown in Table 3, there was a significant positive correlation between FasL expression and lymph node metastasis in oral tumors, suggesting that FasL may be involved in the aggressive clinical behavior and invasive potential of the tumors, and thereby play an important role during oral tumor progression. Taken together, we propose that FasL may play a role in the processes of invasion and metastasis (Zielińska et al, 2008;Bozdogan et al, 2010). In conclusion, our study demonstrates that FasL expression is an early event in oral tumorigenesis, and thus may serve as a marker for early neoplasia and prognosis (Shimonishi et al, 2000).…”

PEG‐liposomal oxaliplatin induces apoptosis in human colorectal cancer cells via Fas/FasL and caspase‐8

“…Activated caspase‐8 cleaves downstream substrates and transmits the death signals from receptors to members of the caspase family, including caspase‐3, caspase‐7 and caspase‐9, finally resulting in apoptosis. (Zielińska et al, 2008; Chen et al, 2009; Peng et al, 2010).…”

Melanoma, Melanin, and Melanogenesis: The Yin and Yang Relationship

“…The killing effects of camptothecin in melanoma cells depended on cell cycle phase with strongest effects on amelanotic than pigmented cells ( 137 ). In this same model, the higher expression of FasL, involved in the induction of cytotoxic T lymphocytes and NK cells death, on pigmented melanoma cells was observed ( 138 ). Furthermore, induced melanogenesis in amelanotic cell line changed the melanoma cells’ morphology and metabolism, decreased the number of cells, and provoked the displacement of cells to the subG0/G1 fraction, indicating the cell death pathway ( 139 – 142 ).…”