Joshi S S, Sinangil F, Sharp J G, Mathews N B, Volsky D J, Brunson K W
Department of Anatomy, University of Nebraska Medical Center, Omaha 68105.
Cancer Detect Prev. 1988;11(3-6):405-17.
In the present investigation we have determined the effects of the differentiation-inducing chemicals dimethyl sulfoxide (DMSO) and sodium butyrate on the growth and tumorigenicity of a highly malignant/metastatic cell line (RAW117-H10) and its less tumorigenic parental lymphoma cell line (RAW117-P). Both of these agents at doses shown to be nontoxic slowed the growth of these cells in suspension culture and significantly lengthened the doubling time while reducing colony formation in the agar tumor stem cell assay. Corresponding to these observations, the in vivo tumorigenicity of the highly malignant RAW117-H10 line was reduced by both chemicals but particularly by butyrate treatment. In addition, both agents increased the expression of some glycoproteins and the glycolipid asialo GM1. There was also a corresponding increase in the NK susceptibility of the normally NK resistant RAW117-H10 cells. To determine if the decreased malignancy of the highly malignant cells following treatment with the chemical agents was primarily due to the alteration in cell surface glycoconjugates or merely due to concomitant decreased growth potential, we transplanted highly glycosylated membrane fragments from normal syngeneic thymocytes to both RAW117-P and RAW117-H10 cells using a Sendai virus mediated membrane fusion technique. The in vivo tumorigenicity of the membrane altered RAW117-H10 cells was significantly decreased. These results strongly suggest that the decreased in vivo malignancy of RAW117-H10 cells resulting from treatment with chemical differentiation agents is caused by their increased susceptibility to NK cell mediated lysis which in turn results from cell surface changes involving altered, primarily increased, expression of certain glycosylated surface molecules. The cell surface glycoconjugates, such as receptors for certain lectins and glycolipid asialo GM1, can be used as markers for malignant potential and NK sensitivity of malignant lymphoid cells.
在本研究中，我们确定了分化诱导化学物质二甲亚砜（DMSO）和丁酸钠对高恶性/转移性细胞系（RAW117-H10）及其致瘤性较低的亲本淋巴瘤细胞系（RAW117-P）的生长和致瘤性的影响。这两种试剂在显示无毒的剂量下，减缓了悬浮培养中这些细胞的生长，显著延长了倍增时间，同时减少了琼脂肿瘤干细胞试验中的集落形成。与这些观察结果相对应，两种化学物质都降低了高恶性RAW117-H10细胞系的体内致瘤性，但丁酸钠处理的效果尤为明显。此外，两种试剂都增加了一些糖蛋白和糖脂去唾液酸GM1的表达。正常情况下对自然杀伤细胞（NK）有抗性的RAW117-H10细胞的NK敏感性也相应增加。为了确定用化学试剂处理后高恶性细胞的恶性程度降低主要是由于细胞表面糖缀合物的改变，还是仅仅由于伴随的生长潜能降低，我们使用仙台病毒介导的膜融合技术，将正常同基因胸腺细胞高度糖基化的膜片段移植到RAW117-P和RAW117-H10细胞中。膜改变的RAW117-H10细胞的体内致瘤性显著降低。这些结果有力地表明，化学分化剂处理导致RAW117-H10细胞体内恶性程度降低是由于它们对NK细胞介导的裂解的敏感性增加，而这又反过来是由于细胞表面变化，主要是某些糖基化表面分子的表达改变，主要是增加。细胞表面糖缀合物，如某些凝集素的受体和糖脂去唾液酸GM1，可作为恶性淋巴细胞恶性潜能和NK敏感性的标志物。
