Postmitotic differentiation of colon carcinoma Caco-2 cells does not prevent reentry in the cell cycle and tumorigenicity
Postmitotic differentiation of colon carcinoma Caco-2 cells does not prevent reentry in the cell cycle and tumorigenicity
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DOI：
10.1006/exmp.2000.2309
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发表时间：
2000-08-01
影响因子：
3.6
通讯作者：
Zweibaum, A
中科院分区：
文献类型：
--
作者：
Pandrea, IV;Carrière, V;Zweibaum, A
我们的目的是分析是否有丝分裂后Caco-2结肠癌细胞，虽然他们表达的终末分化的肠上皮细胞的大部分分化特征，仍然保持，不像正常细胞，增殖潜力。用Caco-2细胞系的克隆TC 7进行实验。分裂的TC 7细胞未分化，并表达可检测水平的胸苷酸合成酶（TS）和细胞色素P450 1A 1（CYP 1A 1）mRNA。当达到汇合时，TS和CYP 1A 1下调，不再检测到有丝分裂，并且发生分化，如通过分化相关标志物mRNA（例如，蔗糖酶-异麦芽糖酶（SI）、二肽基肽酶-IV（DPP-IV）或GLUTS），增加蔗糖酶和DPP-IV的活性，以及在免疫荧光分析中增加细胞层表面上SI的表达。胰蛋白酶消化和接种晚期融合后细胞（第30天）表达完全分化的结果在24小时内上调TS和CYP 1A 1，伴随着显着消失的分化标志物mRNA与蔗糖酶和DPP-IV活性降低，并延迟恢复细胞分裂。随后，在细胞再次达到汇合后，下调TS和CYP 1A 1并恢复细胞分化。分化的细胞去分化的能力进一步证实了伤口的细胞层的晚期融合后分化的培养物：在24小时内，伤口后，细胞从伤口边缘迁移和去分化，如通过透射电子显微镜和消失的SI从迁移细胞的细胞表面所示。晚期融合后分化的细胞在裸鼠体内具有致瘤性。这些结果提出了分化治疗的概念时，适用于结肠癌细胞的有效性的问题。(C)北京大学出版社.
Our purpose was to analyze whether postmitotic Caco-2 colon cancer cells, although they express most of the differentiation characteristics of terminally differentiated intestinal epithelial cells, still maintain, unlike normal cells, a proliferation potential. Experiments were performed with clone TC7 of the Caco-2 cell line. Dividing TC7 cells are undifferentiated and express detectable levels of thymidylate synthase (TS) and cytochrome P450 1A1 (CYP1A1) mRNAs. When reaching confluence TS and CYP1A1 are downregulated, mitosis is no longer detectable, and differentiation takes place, as demonstrated by appearance and increasing levels of differentiation-associated marker mRNAs (e.g., sucrase-isomaltase (SI), dipeptidylpeptidase-IV (DPP-IV) or GLUTS), increasing activities of sucrase and DPP-IV, and increasing expression, on immnofluorescence analysis, of SI on the surface of the cell layer. Trypsinization and seeding of late postconfluent cells (day 30) expressing complete differentiation results within 24 h in upregulation of TS and CYP1A1, a concomitant and dramatic disappearance of differentiation marker mRNAs associated with a decrease in sucrase and DPP-IV activities, and delayed resumption of cell division. This is followed, after the cells have reached confluence again, by downregulation of TS and CYP1A1 and resumption of cell differentiation. The ability of differentiated cells to dedifferentiate was further confirmed by wounding the cell layer of late postconfluent differentiated cultures: within 24 h following the wound, cells migrate from the wound edge and dedifferentiate, as demonstrated by transmission electron microscopy and disappearance of SI from the cell surface of migrating cells. Late postconfluent differentiated cells were tumorigenic in nude mice. These results raise the question of the validity of the concept of differentiation therapy when applied to colon cancer cells. (C) 2000 Academic Press.