Chakrabarty S, Mustain S, Willson J K
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030.
Mol Biother. 1990 Mar;2(1):27-31.
The inducing effect of transforming growth factor-beta (TGF-B) on carcinoembryonic antigen (CEA) secretion and the cellular expression of CEA and CEA crossreactive glycoproteins (CEA-GLY) was examined from a panel of human colonic cell lines with different phenotypic classification. This panel included carcinomas with dissimilar differentiation characteristics and metastatic behavior, and premalignant adenomas derived from colonic polyps. A great degree of heterogeneity was observed in the endogenous levels of CEA secretion and the cellular expression of CEA and CEA-GLY species. The response profiles of the different cell lines to TGF-B treatment were also found to be heterogenous. However, TGF-B was able to induce CEA secretion and up-modulated the cellular expression of CEA and CEA-GLY from a majority of the cells tested. More importantly, TGF-B was able to exert these effects on carcinoma cells that secrete or express minimal or nondetectable amounts of these glycoproteins. These biologic modifying effects of TGF-B may have potential in augmenting the efficacy of CEA as a colon cancer marker, and in antibody-directed radioimaging and therapeutics. Further investigation in vivo in an experimental animal model system is warranted.
从一组具有不同表型分类的人结肠癌细胞系中,研究了转化生长因子-β(TGF-B)对癌胚抗原(CEA)分泌以及CEA和CEA交叉反应糖蛋白(CEA-GLY)细胞表达的诱导作用。该组包括具有不同分化特征和转移行为的癌,以及源自结肠息肉的癌前腺瘤。在CEA分泌的内源性水平以及CEA和CEA-GLY种类的细胞表达中观察到很大程度的异质性。还发现不同细胞系对TGF-B处理的反应谱是异质的。然而,TGF-B能够诱导CEA分泌,并上调大多数测试细胞中CEA和CEA-GLY的细胞表达。更重要的是,TGF-B能够对分泌或表达极少量或无法检测到这些糖蛋白的癌细胞发挥这些作用。TGF-B的这些生物学修饰作用可能在增强CEA作为结肠癌标志物的功效以及抗体导向的放射成像和治疗方面具有潜力。有必要在实验动物模型系统中进行进一步的体内研究。