THE HIGH LYSABILITY BY LAK CELLS OF COLON-CARCINOMA CELLS RESISTANT TO DOXORUBICIN IS ASSOCIATED WITH A HIGH EXPRESSION OF ICAM-1, LFA-3, NCA AND A LESS-DIFFERENTIATED PHENOTYPE
THE HIGH LYSABILITY BY LAK CELLS OF COLON-CARCINOMA CELLS RESISTANT TO DOXORUBICIN IS ASSOCIATED WITH A HIGH EXPRESSION OF ICAM-1, LFA-3, NCA AND A LESS-DIFFERENTIATED PHENOTYPE
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DOI：
10.1002/ijc.2910470521
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发表时间：
1991-03-12
影响因子：
6.4
通讯作者：
PARMIANI, G
中科院分区：
文献类型：
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作者：
RIVOLTINI, L;CATTORETTI, G;PARMIANI, G
对多柔比星 (LoVo/Dx) 具有抗性的人结肠癌细胞亚系 (LoVo/Dx) 先前显示比化学敏感亚系 LoVo/H 更容易被不同的免疫效应子裂解，但据报道，该亚系同样容易受到可溶性细胞因子（TNF-α 和/或 IFN-gamma）的直接抗增殖作用的影响。 LoVo/Dx 上表达的粘附分子 ICAM-I、LFA-3 和 NCA 多于 LoVo/H，而在任一肿瘤亚系的细胞表面或培养上清液中均未检测到显着量的 CEA。抗 ICAM-I、抗 LFA-3 和抗 NCA 单克隆抗体 (MAb) 导致 LoVo/Dx 的白介素 2 (IL-2) 活化淋巴细胞 (LAK) 裂解显着减少，而对 LoVo/H 的作用较低。这些抗体的组合能够进一步增强对两个亚系的 LAK 裂解的抑制。通过形态学、体外生长、标记物（例如桥粒斑蛋白和波形蛋白）表达的改变或增加以及粘蛋白的消失来评估，LoVo/Dx 显示出分化程度较低的表型。用分化剂（二甲基甲酰胺和维甲酸）处理 LoVo 亚系会导致所研究的所有粘附分子的表达减少，同时对 LAK 介导的裂解的抵抗力增加。这些数据表明，化疗耐药肿瘤细胞对细胞毒性效应物的敏感性取决于粘附分子（包括NCA）的表达水平，并且与分化阶段相关。
A human colon-carcinoma cell subline resistant to doxorubicin (LoVo/Dx), previously shown to be more lysed than the chemosensitive subline LoVo/H by different immune effectors, is reported here to be similarly susceptible to direct, anti-proliferative effect of soluble cytokines (TNF-alpha and/or IFN-gamma). More adhesion molecules ICAM-I, LFA-3 and NCA were expressed on LoVo/Dx than on LoVo/H, while no significant amounts of CEA were detectable on the cell surface or in culture supernatant of either tumor subline. Anti-ICAM-I, anti-LFA-3 and anti-NCA monoclonal antibodies (MAbs) caused a marked reduction of lysis by interleukin-2 (IL-2) activated lymphocytes (LAK) of LoVo/Dx, whereas a lower effect was evident on LoVo/H. A pool of these antibodies was able to further increase the inhibition of the LAK lysis of both sublines. LoVo/Dx displayed a less differentiated phenotypes as assessed by morphology, in vitro growth and altered or increased expression of markers such as desmoplakin and vimentin respectively, and disappearance of mucin. Treatment of LoVo sublines with differentiating agents (dimethylformamide and retionic acid) led to a decreased expression of all adhesion molecules studied, accompanied by increased resistance to LAK-mediated lysis. These data indicate that sensitivity of chemoresistant tumor cells to cytotoxic effectors depends on the level of expression of adhesion molecules, including NCA, and is related to differentiation stage.