Unique characteristics of rectal carcinoma cell lines derived from invasive carcinomas in ulcerative colitis patients
Unique characteristics of rectal carcinoma cell lines derived from invasive carcinomas in ulcerative colitis patients
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DOI：
10.1111/j.1349-7006.2004.tb02205.x
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发表时间：
2004-03-01
期刊：
影响因子：
5.7
通讯作者：
Okayasu, I
中科院分区：
文献类型：
--
作者：
Yamashita, K;Yasuda, S;Okayasu, I
为了确定溃疡性结肠炎（UC）相关癌的特征，将8个病变（高度发育不良和浸润性癌）植入严重联合免疫缺陷（SCID）小鼠和/或体外培养。由高度异型增生组成的粘膜内肿瘤在植入后表现出极其缓慢的增殖（2/3例），体外培养失败（4例）。然而，浸润性癌在SCID小鼠植入后和体外均表现出快速生长（4/4例）。从两例浸润性癌中，建立了6个细胞系，这些是文献中首次描述的。除了甲胎蛋白、嗜铬粒蛋白A和雌激素受体的免疫化学确定的表型表达的变化之外，建立的细胞系还显示出不同的分化（中度或低分化腺癌、腺鳞癌和低分化腺癌伴多核巨细胞和骨形成）。结果与散发性结直肠癌的结果相反。虽然DPC-4的DNA变异并不常见，但在6个细胞系中均发现DPC-4的17 p和18 q杂合性缺失和8 ~ 11号外显子缺失，表明其具有较高的遗传不稳定性。我们发现了许多染色体（#3、5、6、8、10、11、13、16、17、18和19）的丢失或易位，而不是染色体1、5、8、11、13、17和18，其经常涉及散发性结直肠癌细胞系。因此，建立的细胞系可能是慢性炎症-癌序列中肿瘤发生和进展的良好模型。
To identify the characteristics of ulcerative colitis (UC)-associated carcinomas, 8 lesions, high-grade dysplasias and invasive carcinomas, were implanted into severely combined immunodeficient (SCID) mice and/or cultured in vitro. Intramucosal neoplasias consisting of high-grade dysplasia showed extremely slow proliferation after implantation (2/3 cases) and in vitro culture failed (4 cases). However, invasive carcinomas demonstrated rapid growth both after SCID mouse implantation and in vitro (4/4 cases). From two cases of invasive carcinomas, 6 cell lines were established, and these are the first to be described in the literature. In addition to variation in immunohistochemically determined phenotypic expression regarding alpha-fetoprotein, chromogranin A and estrogen receptors, the established cell lines showed varying differentiation (moderately or poorly differentiated adenocarcinoma, adenosquamous carcinoma and poorly differentiated adenocarcinoma with multinuclear giant cells and bone formation). The results are in contrast with findings for sporadic colorectal carcinomas. Although the prevalence of DNA alterations is not frequent, loss of heterozygosity (17p and 18q) and deletion of exons 8 to 11 in DPC-4 were revealed in all of 6 cell lines, suggesting relatively high genetic instability. We found loss or translocation of many chromosomes (#3, 5, 6, 8, 10, 11, 13, 16, 17, 18 and 19) other than chromosomes 1, 5, 8, 11, 13, 17 and 18, which are frequently involved in sporadic colorectal carcinoma cell lines. Thus, the established cell lines may be good models of tumorigenesis and progression in the chronic inflammation-carcinoma sequence.