Haynes L W, Weller R O
Br J Exp Pathol. 1978 Jun;59(3):259-76.
Explants from 18 gliomas were cultured for periods up to 7 weeks and studied by light microscopy scanning and transmission electron microscopy. Well-differentiated tumor tissue gave rise to early outgrowths of stellate cells showing process orientation. Poorly-differentiated tissue produced a more haphazard out-growth of pleomorphic cells with few processes and flattened pseudopodia. Mean circadian cell displacement was several times greater in poorly-differentiated cells, but was significantly and reversibly reduced by treatment and dibutyryl cAMP (5 X 10(-4)M) for 48 h. Reduction in motility was directly correlated with a change in cell morphology to a more stellate form. Well-differentiated cells had a smooth surface with ruffling restricted to the ends of processes and highly orientated glial filament and microfilament bundles. The poorly-differentiated cell surface had a microvillous, blebbed appearance and ruffling regularly occurred around the edge of the cytoplasm. Glial filaments and microfilaments were fewer and less well orientated in the poorly-differentiated cells; sites of adhesion to the substratum were fewer than in well-differentiated cells. Treatment of malignant cultures with dibutyryl cAMP resulted in smoothing of the cell surface, retraction of processes into thin pseudopodia and the appearance of microfilament bundles within the cells. These features marked the apparent cyto-differentiation. However, there was a loss of attachment, disappearance of microtubules and loss of glial filaments in the cytoplasm which was not compatible with differentiation. Intracellular recordings of membrane potentials gave a significantly higher mean value for well-differentiated cells. The mean membrane potential and input resistance of poorly-differentiated cells was unchanged by the addition of dibutyryl cAMP. The results of this study suggest that some, but not all, features of mature glia are restored in malignant tumour cells by cAMP treatment.
取自18例神经胶质瘤的外植体培养长达7周，并通过光学显微镜扫描和透射电子显微镜进行研究。分化良好的肿瘤组织产生了呈放射状排列的早期星状细胞生长。分化不良的组织产生了多形性细胞的更不规则生长，其突起少且有扁平伪足。分化不良的细胞中平均昼夜细胞位移大几倍，但经处理和用二丁酰环磷腺苷（5×10⁻⁴M）处理48小时后显著且可逆地降低。运动性的降低与细胞形态转变为更星状的形式直接相关。分化良好的细胞表面光滑，褶皱仅限于突起末端，且有高度定向的胶质丝和微丝束。分化不良的细胞表面有微绒毛、泡状外观，且在细胞质边缘经常出现褶皱。分化不良的细胞中胶质丝和微丝较少且排列不太整齐；与基质的粘附位点比分化良好的细胞少。用二丁酰环磷腺苷处理恶性培养物导致细胞表面变光滑，突起缩回形成细伪足，且细胞内出现微丝束。这些特征标志着明显的细胞分化。然而，出现了附着丧失、微管消失以及细胞质中胶质丝丧失，这与分化不相符。膜电位的细胞内记录显示分化良好的细胞平均数值显著更高。添加二丁酰环磷腺苷后，分化不良的细胞平均膜电位和输入电阻未改变。本研究结果表明，通过环磷腺苷处理，恶性肿瘤细胞中成熟神经胶质细胞的一些而非全部特征得以恢复。
