Blottière H M, Zennadi R, Grégoire M, Aillet G, Denis M G, Meflah K, Le Pendu J
CJF INSERM 90-11, Institut de biologie, Nantes, France.
Int J Cancer. 1993 Feb 1;53(3):409-17. doi: 10.1002/ijc.2910530311.
NK and LAK cells which are able to lyse tumor target cells in an MHC-unrestricted manner are not equally effective against targets of the same nature. In the case of colorectal tumors, some cells are highly sensitive, whereas others are resistant to NK and can even be quite resistant to LAK-mediated lysis. In the present paper, we tried to correlate the stage of differentiation of 17 human colorectal tumor cell lines with their NK- or LAK-cell susceptibility. It was observed that NK cells killed colorectal target cells independently from their stage of differentiation defined according to histopathological criteria from xenografting in nude mice. NK susceptibility was not correlated either with in vitro-defined criteria of differentiation, such as cell polarity and morphology, brush-border enzyme expression and CEA production. A LAK-resistant HT-29 sub-line (HT-29 LAK) was selected which could not be distinguished from HT-29 in terms of features of differentiation. It was further observed that HT-29 Glc-/+ cell line, a highly differentiated enterocytic-like variant of HT-29, obtained after glucose starvation, was killed by LAK cells as efficiently as the moderately differentiated parental HT-29, and that Caco-2 cells, which differentiate spontaneously after confluence in standard culture conditions, were equally sensitive to NK-mediated lysis whatever their stage of differentiation. In contrast, HT29 MTX10(-5), a highly differentiated mucus-secreting variant of HT29 obtained by methotrexate selection, was much more resistant to LAK cells than parental HT29 cells.
能够以MHC非限制性方式裂解肿瘤靶细胞的NK细胞和LAK细胞对相同性质的靶细胞的作用效果并不相同。就结直肠肿瘤而言，一些细胞对NK细胞高度敏感，而另一些细胞则对NK细胞具有抗性，甚至对LAK介导的裂解作用也相当耐受。在本论文中，我们试图将17种人结直肠肿瘤细胞系的分化阶段与其对NK细胞或LAK细胞的敏感性相关联。据观察，NK细胞杀死结直肠靶细胞的作用与其根据裸鼠异种移植的组织病理学标准所定义的分化阶段无关。NK细胞敏感性也与体外定义的分化标准无关，如细胞极性和形态、刷状缘酶表达及癌胚抗原产生。我们筛选出了一株对LAK细胞有抗性的HT - 29亚系（HT - 29 LAK），其在分化特征方面与HT - 29无法区分。进一步观察到，HT - 29 Glc - / +细胞系是HT - 29经葡萄糖饥饿处理后获得的一种高度分化的肠上皮样变体，它被LAK细胞杀死的效率与中度分化的亲代HT - 29相同，并且在标准培养条件下汇合后能自发分化的Caco - 2细胞，无论其分化阶段如何，对NK介导的裂解作用同样敏感。相比之下，HT29 MTX10(-5)是通过甲氨蝶呤筛选获得的HT29的一种高度分化且分泌黏液的变体，它比亲代HT29细胞对LAK细胞的抗性要强得多。
