Regulation of carcinoembryonic antigen expression in different human colorectal tumor cells by interferon-gamma.
Regulation of carcinoembryonic antigen expression in different human colorectal tumor cells by interferon-gamma.
复制标题
干扰素-γ对不同人结直肠肿瘤细胞中癌胚抗原表达的调节。
作者：
F. Guadagni;P. Witt;P. Robbins;J. Schlom;J. Greiner
本文研究了重组人干扰素-γ对7种不同分化阶段的人结直肠癌细胞系癌胚抗原(CEA)表达的调节。其中两个结直肠癌细胞系分化较差，不表达CEA。然而，干扰素处理诱导了其中一个细胞系(即DLD-1)的CEA表达，其证据是CEA相关的mRNA转录产物的出现，以及通过流式细胞仪和放射免疫分析检测到的细胞表面抗原的表达。在高分化结直肠肿瘤细胞系中，干扰素-γ处理对全细胞提取液中CEA含量和细胞表面CEA表达阳性细胞的百分率无明显影响。事实上，干扰素-γ处理高分化的LS174T细胞不仅不能改变CEA的表达，而且也不能诱导人类II类白细胞抗原的表达。因此，高分化的LS174T细胞系和低分化的MIP细胞系代表了对干扰素-γ诱导肿瘤(即CEA)或正常(即人类白细胞抗原I类和II类)表面抗原表达变化无反应的结直肠癌细胞类型。对干扰素-γ改变CEA表达能力最敏感的是中分化细胞系(如HT-29、WiDR等)。经干扰素-γ处理后，细胞提取物中CEA含量增加了300-400%，细胞表面CEA表达阳性的细胞比例从30-45%增加到80%以上。用7株结直肠癌细胞株中的4株研究了干扰素对2‘，5’-寡腺苷合成酶(2‘-5’-A)活性的影响。结构性2‘-5’A活性变化约14倍，与细胞分化程度无关。干扰素-γ处理后，4种结直肠癌细胞的2‘-5’A活性均升高。特别是，增强MIP和LS174T细胞中2‘-5’A活性的能力，明显地将调节2‘-5’A活性的细胞事件与参与调节细胞表面抗原表达的细胞事件区分开来。这些发现还表明，干扰素-γ对CEA表达的调节与细胞分化的程度无关，此外，还提供了一些信息，表明在使用单抗的佐剂环境中，哪些人类肿瘤细胞群可能最容易受到干扰素-伽马的肿瘤抗原增强。
The regulation of carcinoembryonic antigen (CEA) expression by recombinant human interferon-gamma (IFN-gamma) was studied in a series of 7 human colorectal tumor cell lines at various stages of differentiation. Two of the colorectal cell lines were poorly differentiated and did not constitutively express CEA. IFN-gamma treatment, however, induced CEA expression in one of those lines (i.e., DLD-1) as evidenced by the appearance of CEA-related mRNA transcripts, as well as the cell surface expression of the antigen as measured by flow cytometry and radioimmunoassay. In the highly differentiated colorectal tumor cell lines, IFN-gamma treatment resulted in no detectable change in CEA content in whole cell extracts or in the percentage of cells positive for cell surface CEA expression. In fact, IFN-gamma treatment of the highly differentiated LS174T cell line not only failed to alter CEA expression, but also failed to induce class II human leukocyte antigen expression. Therefore, the highly differentiated LS174T cell line and the poorly differentiated MIP cell line represent colorectal tumor cell types that are unresponsive to the ability of IFN-gamma to induce alterations in tumor (i.e., CEA) or normal (i.e., class I and class II human leucocyte antigen) surface antigen expression. The most responsive of human colorectal tumor cells to the ability of IFN-gamma to alter CEA expression were the moderately differentiated cell lines (i.e., HT-29, WiDr, etc.). IFN-gamma treatment of those cell types increased the CEA content in cell extracts by 300-400%, and increased the percentage of cells positive for surface CEA expression from 30-45% to greater than 80%. The effect of IFN-gamma treatment on 2',5'-oligoadenylate synthetase (2'-5' A) activity was also studied using 4 of the 7 colorectal cell lines. Constitutive 2'-5' A activity varied approximately 14-fold and was not correlated with degree of cellular differentiation. IFN-gamma treatment increased 2'-5' A activity in all 4 colorectal tumor cells tested. In particular, the ability to enhance 2'-5' A activity in the MIP and LS174T cells, 2 colorectal tumor cell types that previously were shown to be unresponsive to IFN-gamma-mediated changes in their antigenic phenotype, clearly separates cellular events regulating 2'-5' A activity from those involved in regulating cell surface antigen expression. The findings also suggested that the regulation of CEA expression by IFN-gamma is not related to the degree of cellular differentiation and, furthermore, provide some insight into which human tumor cell populations may be the most amenable to tumor antigen augmentation by IFN-gamma in an adjuvant setting with a monoclonal antibody.
登录
查看更多内容
未分化人结肠癌细胞系 (MIP-101) 的分离和表征。
影响因子：
2.4
作者：
Niles,RM;Wilhelm,SA;SteeleJr,GD;Burke,B;Christensen,T;Dexter,D;O'Brien,MJ;Thomas,P;Zamcheck,N
通讯作者：
Zamcheck,N
干扰素对人乳腺癌和卵巢癌细胞系中主要组织相容性复合物编码和非主要组织相容性复合物编码抗原的差异诱导。
影响因子：
11.2
作者：
Boyer,CM;Dawson,DV;Neal,SE;Winchell,LF;Leslie,DS;Ring,D;BastJr,RC
通讯作者：
BastJr,RC
环腺苷 3:5-单磷酸对人结肠癌细胞糖蛋白和癌胚抗原合成和释放的影响。
影响因子：
11.2
作者：
Hwang,WI;Sack,TL;Kim,YS
通讯作者：
Kim,YS
111In标记抗癌胚抗原单克隆抗体对结直肠癌的术前显像。
影响因子：
11.2
作者：
Beatty,JD;Duda,RB;Williams,LE;Sheibani,K;Paxton,RJ;Beatty,BG;Philben,VJ;Werner,JL;Shively,JE;Vlahos,WG
通讯作者：
Vlahos,WG
通过转化生长因子-β 诱导癌胚抗原分泌并调节人结肠癌细胞中的蛋白质分泌/表达和纤连蛋白/层粘连蛋白表达。
影响因子：
11.2
作者：
Chakrabarty,S;Tobon,A;Varani,J;Brattain,MG
通讯作者：
Brattain,MG