Fas和Fas ligand (FasL; CD95L; Apo-1L)的結合會誘發部份表現Fas的細胞凋亡(apoptosis)。以前的研究認為腫瘤細胞表現FasL (tumor FasL)以躲避免疫系統的攻擊。但是，腫瘤細胞表現FasL如何影響腫瘤的生長及轉移，至目前仍不清楚。本實驗利用FasL特定的核醣酵素(FasL-specific ribozyme; FasLRibozyme)來抑制FasL基因的表現，並且建立帶有FasL特定的核醣酵素的B16F10黑色素癌細胞株(FasL表現低腫瘤細胞；FasLlow tumor cells；FasLR)，應用於皮下腫瘤形成及腫瘤細胞轉移至肺部的動物實驗，分析腫瘤細胞的FasL表現量和腫瘤細胞的生長和轉移之相關性。所建立的FasL表現量高(FasLhigh)和FasL表現量低(FasLlow)細胞株的Fas和腫瘤壞死因子-(tumor necrosis factor-; TNF-的基因表現量並無差異。
當腫瘤細胞株以皮下方式植入小鼠體內，雖然FasL可以促進嗜中性球浸潤及腫瘤細胞的凋亡(apoptosis)。FasL表現量低(FasLlow)細胞株在皮下形成腫瘤的速率比FasL表現量高(FasLhigh)細胞株慢。在缺乏嗜中性球小鼠的體內，FasL表現量低(FasLlow)細胞株的生長顯著大於在正常小鼠體內的生長速率。相對地，FasL表現量高(FasLhigh)細胞株腫瘤的生長，在嗜中性球正常或是缺乏的小鼠體內，並無顯著差異。局部注射脂多醣(LPS)至C57BL/6及NOD/SCID小鼠的腫瘤區域，顯著抑制FasL表現量低(FasLlow)細胞株的生長，而對於FasL表現量高(FasLhigh)細胞株的生長抑制作用較為輕微。
在生體外將腫瘤細胞和嗜中性球一起培養，嗜中性球都能毒殺FasL表現量高(FasLhigh)和FasL表現量低(FasLlow)細胞株。FasL表現量高(FasLhigh)細胞株對於嗜中性球所誘發的細胞凋亡(apoptosis)，比FasL表現量低(FasLlow)細胞株具有耐受性。腫瘤細胞表現FasL會抑制嗜中性球的明膠酵素B (gelatinase B)的分泌、氧活性物質(reactive oxygen species; ROS)的產生及CD11b的表現。因此，腫瘤細胞表現FasL導致嗜中性球不活化的作用機制，可能是皮下腫瘤細胞在躲避免疫系統攻擊的原因之一。
如果將腫瘤細胞株以尾靜脈注射至小鼠體內，FasL表現量低(FasLlow)細胞株轉移至肺臟的數目明顯高於FasL表現量高(FasLhigh)細胞株。在腫瘤細胞侵入肺部時，腫瘤細胞表現FasL也能促進嗜中性球浸潤及腫瘤細胞細胞的凋亡(apoptosis)。利用抗體去除小鼠體內的嗜中性球，可以明顯促進FasL表現量高(FasLhigh)和FasL表現量低(FasLlow)細胞株轉移至肺臟。
總之，腫瘤細胞表現Fas-L的確會影響腫瘤的生長，但是其效益會因腫瘤形成的器官或組織而有不同。

Fas (CD95) and Fas ligand interaction induces apoptosis in Fas+ cells of many cell types. The expression of FasL on tumor cells (tumor FasL) has been implicated in evasion of immune surveillance. How Fas-L on tumors affects tumorigenesis and metastasis, however, is not clear. In this study, we have established B16F10 melanoma-derived cells carrying either plasmid encoding FasL specific ribozyme (FasLR; FasLlow tumor cells) or vector plasmid (FasLhigh tumor cells) to investigate the role of Fas-L in tumorigenicity and metastasis. FasLR suppressed the expression of FasL but not Fas or TNF- in B16F10 melanoma cells. When injected subcutaneously into C57BL/6 mice, FasLlow tumor cells grew slowly than did FasLhigh melanoma. FasLhigh tumor cells showed more intensive neutrophilic infiltration accompanied by multiple necrotizing areas than did FasLlow tumor. The average size of FasLlow tumors, but not that of FasLhigh tumors, was significantly enhanced in mice depleted of neutrophils. Consistently, a local injection of LPS to recruit/activate neutrophils significantly delayed tumor formation of FasLlow tumor cells, and slightly retarded that of FasLhigh tumor cells in both C57BL/6 and NOD/SCID mice.
Neutrophils killed FasLlow melanoma cells more effective than FasLhigh melanoma cells in vitro. The resistance of FasLhigh melanoma cells to being killed by neutrophil was correlated with impaired neutrophil activation as demonstrated by reductions in gelantinase B secretion, ROS production, and the surface expression of CD11b and the transcription of FasL. Local transfer of casein-enriched or PMA-treated neutrophils delayed tumor formation by melanoma cells. Thus, inactivation of neutrophils by tumor FasL is an important mechanism by which tumor cells escape immune attack.
On the other hand, suppression of FasL in B16F10 melanoma cells by FasLR enhanced lung metastasis of the cells in C57BL/6 mice, and that was correlated with reductions in both apoptotic tumor cells and granulocytic infiltration. Mice depleted of granulocytes, but not CD4+ and CD8+ cells, showed a greatly elevated susceptibility to lung metastasis. Moreover, apoptosis in tumor cells was significantly reduced in granulocyte-depleted mice during the course of tumor formation.
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