Selection of invasive and metastatic subpopulations from a human lung adenocarcinoma cell line

Selection of invasive and metastatic subpopulations from a human lung adenocarcinoma cell line
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DOI:
10.1165/ajrcmb.17.3.2837
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发表时间:
1997-09-01
影响因子:
6.4
通讯作者:
Wu, CW
Wu, CW
中科院分区:
医学1区
文献类型:
--
作者:
Chu, YW;Yang, PC;Wu, CW

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为了更好地理解肺癌侵袭和转移的机制,使用Transwell侵袭室从人肺腺癌CL 1的克隆细胞系中选择侵袭性更强的癌细胞群。通过该体外选择过程获得了具有进行性侵袭力的五个亚系,命名为CL 1 -1、CL 1 -2、CL 1 -3、CL 1 -4和CL 1 -5。它们通过基底膜基质的侵袭能力比亲本细胞增加4- 6倍。此外,在严重联合免疫缺陷(SCID)小鼠中,亚系表现出其在软琼脂上的集落形成能力、致瘤性和转移潜能的增加。检查细胞系的表型显示92 kD明胶酶的表达增加,并且用抗角蛋白-8和-18抗体染色的细胞群增加。克隆分离的抗角蛋白-18抗体阳性和阴性细胞群体表现出相关的增强这些细胞的侵袭性和角蛋白-18的表达。这些结果支持了这样的观点,即肺癌细胞的转移行为可以用这种体外系统来表征,并且可以克隆地研究这些进行性侵袭性癌细胞的性质。
To better understand the mechanism(s) underlying lung cancer invasion and metastasis, a Transwell invasion chamber was used to select progressively more invasive cancer cell populations from a clonal cell line of human lung adenocarcinoma, CL1. Five sublines with progressive invasiveness, designated CL1-1, CL1-2, CL1-3, CL1-4, and CL1-5, were obtained through this in vitro selection process. Their invasive abilities through basement membrane matrix showed a 4- to 6-fold increase over that of the parental cells. Moreover, the sublines manifested an increase in their colony-forming ability on soft agar, tumorigenicity, and metastatic potency in severe combined immunodeficiency (SCID) mice. Examining the phenotypes of the cell lines revealed increased expression of 92 kD gelatinase and an increase in the cell population stained with anti-keratin-8 and -18 antibodies. Clonal isolation of anti-keratin-18-antibody-positive and negative cell populations demonstrated a correlated enhancement of the invasiveness of these cells and their expression of keratin-18. These results support the notion that the metastatic behavior of lung cancer cells can be characterized with this in vitro system, and that the properties of these progressively invasive cancer cells can be clonally studied.