Release of carcinoembryonic antigen from human colon cancer cells by phosphatidylinositol-specific phospholipase C.
Release of carcinoembryonic antigen from human colon cancer cells by phosphatidylinositol-specific phospholipase C.
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磷脂酰肌醇特异性磷脂酶 C 从人结肠癌细胞中释放癌胚抗原。
DOI：
10.1172/jci113636
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Kim,YS
中科院分区：
文献类型：
--
作者：
Sack,TL;Gum,JR;Low,MG;Kim,YS
癌胚抗原(CEA)从结肠癌细胞释放到循环中，在那里临床上监测它是癌症复发或进展的指标。我们用人结肠腺癌细胞系LS-174T、人结肠癌标本和结肠癌患者血清研究了CEA膜附着和释放的机制。CEA在体外和体内的释放与CEA从膜结合的疏水分子转化为可溶的亲水形式有关，而分子质量没有明显的下降。当LS-174T细胞膜与不同的缓冲液、蛋白酶和磷脂酶孵育时，释放CEA并将其转化为亲水性的唯一试剂是磷脂酰肌醇特异性磷脂酶C(PI-PLC)的制剂。[3 H]乙醇胺和[3 H]棕榈酸酯都能被代谢地结合到CEA中，但PI-PLC处理只释放棕榈酸酯，这与糖基-磷脂酰肌醇的存在是一致的。PI-PLC治疗还可以从活体单层和七个人结肠癌标本中释放大量CEA。这些实验表明，细胞CEA通过与膜磷脂酰肌醇分子的共价键连接到膜上，内源性磷脂酶可能对体外和活体释放CEA起重要作用。
Carcinoembryonic antigen (CEA) is released from colon cancer cells into the circulation where it is monitored clinically as an indicator of the recurrence or progression of cancer. We have studied the mechanism of CEA membrane attachment and release using the human colonic adenocarcinoma cell line LS-174T, specimens of human colon cancers, and serum from colon cancer patients. CEA release by cells in vitro and in vivo is associated with the conversion of CEA from a membrane-bound, hydrophobic molecule to a soluble, hydrophilic form with no apparent decrease in molecular mass. When LS-174T cell membranes were incubated with various buffers, proteases, and phospholipases, the only agents that released CEA and converted it to the hydrophilic form were preparations of phosphatidylinositol-specific phospholipase C (PI-PLC). Both [3H]ethanolamine and [3H]palmitate could be incorporated metabolically into CEA but only palmitate was released by treatment with PI-PLC, consistent with the presence of a glycosyl-phosphatidylinositol linkage. PI-PLC treatment also release significant quantities of CEA from living monolayers and from seven human colon cancer specimens. These experiments suggest that cellular CEA is anchored to membranes by a covalent linkage to a membrane phosphatidylinositol molecule, and that an endogenous phospholipase may be important for releasing CEA in vitro and in vivo.Images