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腺瘤和癌衍生上皮细胞系中癌胚抗原的表达:肿瘤进展的可能标志物及丁酸钠对表达的调节

Expression of carcinoembryonic antigen by adenoma and carcinoma derived epithelial cell lines: possible marker of tumour progression and modulation of expression by sodium butyrate.

作者信息

Berry R D, Paraskeva C

机构信息

Department of Pathology, Medical School, University Walk, Bristol, UK.

出版信息

Carcinogenesis. 1988 Mar;9(3):447-50. doi: 10.1093/carcin/9.3.447.

Abstract

We have used an indirect immunofluorescence assay to demonstrate the cell membrane expression of carcinoembryonic antigen (CEA) by a pre-malignant colorectal adenoma derived epithelial cell line (PC/AA) and three colorectal carcinoma cell lines (HT29, PC/JW and PC/JW/FI). The results obtained indicated that CEA may be used as a marker for tumour progression up to the point of malignant transformation, after which the selection for anaplastic variants during continuous in vitro culture may result in the subsequent reduction of cell membrane CEA expression. The percentage of PC/AA cells expressing cell membrane CEA increased from 23.1% of diploid early passage (passage 18) cells to 56.0% of aneuploid late passage (passage 58) cells. Although non-tumorigenic, the proportion of PC/AA cells expressing cell membrane CEA at late passage corresponded to that for the PC/JW carcinoma line (56.2%) and is further evidence for the progression of PC/AA in culture. A 3T3 feeder-independent variant of PC/JW (PC/JW/FI) demonstrated a similar percentage of CEA-positive cells as the parental line for the first 21 passages without feeder support, but by passage 27 without 3T3 feeders only 35.3% of cells stained positive. This could be restored to 62.0% by continuous treatment with sodium butyrate (2 mM). A differential growth response to sodium butyrate was noted for the pre-malignant adenoma cell line PC/AA and the carcinoma lines HT29 and PC/JW/FI. Concentrations of sodium butyrate (2 mM) that killed early passage PC/AA cells allowed the late passage PC/AA cells and the carcinoma lines to proliferate, raising the possibility of sodium butyrate acting as a tumour promotor in the human colorectum.

摘要

我们使用间接免疫荧光测定法,来证实一种癌前结肠直肠腺瘤衍生上皮细胞系(PC/AA)以及三种结肠直肠癌细胞系(HT29、PC/JW和PC/JW/FI)细胞膜上癌胚抗原(CEA)的表达。所得结果表明,CEA可用作肿瘤进展直至恶性转化点的标志物,在此之后,在连续体外培养过程中对间变变体的选择可能会导致随后细胞膜CEA表达的降低。表达细胞膜CEA的PC/AA细胞百分比,从二倍体早期传代(第18代)细胞的23.1%增加至非整倍体晚期传代(第58代)细胞的56.0%。尽管PC/AA细胞无致瘤性,但晚期传代时表达细胞膜CEA的PC/AA细胞比例与PC/JW癌细胞系(56.2%)相当,这进一步证明了PC/AA在培养中的进展。PC/JW的一种不依赖3T3饲养层的变体(PC/JW/FI),在前21代无饲养层支持的情况下,CEA阳性细胞百分比与亲代细胞系相似,但在第27代无3T3饲养层时,只有35.3%的细胞染色呈阳性。通过用丁酸钠(2 mM)连续处理,这一比例可恢复至62.0%。癌前腺瘤细胞系PC/AA以及癌细胞系HT29和PC/JW/FI对丁酸钠呈现出不同的生长反应。杀死早期传代PC/AA细胞的丁酸钠浓度(2 mM),却能使晚期传代PC/AA细胞和癌细胞系增殖,这增加了丁酸钠在人类结肠直肠中充当肿瘤促进剂的可能性。

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