2 NEW HUMAN CHOLANGIOCARCINOMA CELL-LINES AND THEIR CYTOGENETICS AND RESPONSES TO GROWTH-FACTORS, HORMONES, CYTOKINES OR IMMUNOLOGICAL EFFECTOR-CELLS
2 NEW HUMAN CHOLANGIOCARCINOMA CELL-LINES AND THEIR CYTOGENETICS AND RESPONSES TO GROWTH-FACTORS, HORMONES, CYTOKINES OR IMMUNOLOGICAL EFFECTOR-CELLS
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DOI：
10.1002/ijc.2910520217
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发表时间：
1992-09-09
影响因子：
6.4
通讯作者：
WHITESIDE, TL
中科院分区：
文献类型：
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作者：
SHIMIZU, Y;DEMETRIS, AJ;WHITESIDE, TL
建立了2个新的人胆管癌细胞系（CC- sw - i和CC- lp - i），并在培养中维持2年。组织学上，两例原肝肿瘤均为腺癌，细胞系表现为中分化腺癌的形态学特征。免疫组化结果显示，两种细胞系的细胞角蛋白AEI均呈强阳性，而碳水化合物肿瘤相关抗原CA19-9呈阴性。两种细胞系的超微结构分析显示存在紧密的连接复合物和局部形成的微绒毛。两种CC细胞系在裸鼠体内均具有致瘤性。细胞遗传学分析表明，这两种细胞系表达高度非整倍体核型，具有许多结构和数值偏差。cc - sw - 1是次二倍体，有大量染色体丢失和结构重排，而cc - lp - 1是超二倍体，有多条额外的染色体。在15%胎牛血清的作用下，cc - sw - 1和cc - lp - 1细胞株的增殖时间分别为72小时和180小时。胰岛素能显著刺激cc - sw - 1细胞株的生长，而表皮生长因子（EGF）能显著增强cc - lp - 1细胞株的生长。相反，地塞米松以剂量依赖的方式强烈抑制两种细胞系的增殖。在多种重组细胞因子对CC细胞系生长或表面抗原表达的影响中，只有白细胞介素i - β (il - β)强烈抑制CC- lp - i细胞系的生长，而干扰素（IFNs）或肿瘤坏死因子α (tnf - α)具有轻度抑制作用。两种肿瘤细胞系均对自然杀伤细胞（NK）有抗性，但对淋巴因子激活杀伤细胞（LAK）敏感。用ifn - γ、ifn - α或tnf - α对肿瘤细胞进行预孵育可显著降低各肿瘤细胞系对LAK细胞裂解的敏感性，敏感性的变化与肿瘤细胞表面HLA抗原或细胞间粘附分子- i （ICAM-I）的表达无关。这2个CC细胞系有望为人类CC细胞生物学提供有价值的信息。
Two new human cholangiocarcinoma (CC) cell lines (CC-SW-I and CC-LP-I) were established and maintained in culture for 2 years. Histologically, both original liver tumors were adenocarcinomas, and the cell lines exhibited morphologic features of moderately differentiated adenocarcinoma. Immunohistochemistry showed that both cell lines were strongly positive for cytokeratin AEI but negative for carbohydrate tumor-associated antigen, CA19-9. Ultrastructural analysis of both cell lines showed the presence of tight junctional complexes and focally formed microvilli. Both CC cell lines were tumorigenic in nude mice. Cytogenetic analysis showed that both cell lines expressed highly aneuploid karyotypes with numerous structural and numerical deviations. CC-SW-I was hypodiploid with numerous chromosome losses and structural rearrangements, while CC-LP-I was hyperdiploid and displayed multiple additional chromosomes. Doubling times for the CC-SW-I and CC-LP-I cell lines in the presence of 15% fetal bovine serum were 72 hr and 180 hr, respectively. Growth of the CC-SW-I cell line was significantly stimulated in the presence of insulin, while that of the CC-LP-I cell line was significantly augmented by epidermal growth factor (EGF). In contrast, dexamethasone strongly inhibited proliferation of both cell lines in a dose-dependent manner. Among various recombinant cytokines examined for effects on growth or surface antigen expression on CC cell lines, only interleukin I-beta (ILI-beta) strongly inhibited growth of the CC-LP-I cell line, while interferons (IFNs) or tumor necrosis factor-alpha (TNF-alpha) were mildly inhibitory. Both tumor cell lines were resistant to natural killer (NK) cells but sensitive to lymphokine-activated killer (LAK) cells. Preincubation of tumor cells with IFN-gamma, IFN-alpha or TNF-alpha significantly decreased the susceptibility of each tumor cell line to lysis by LAK cells, and the change in sensitivity did not correlate with the expression of HLA antigens or intercellular adhesion molecule-I (ICAM-I) on the surface of tumor cells. These 2 CC cell lines are expected to provide valuable information about cell biology of human CC.