Van Muijen G N, Cornelissen L M, Jansen C F, Figdor C G, Johnson J P, Bröcker E B, Ruiter D J
Department of Pathology, University Hospital Nijmegen, The Netherlands.
Clin Exp Metastasis. 1991 May-Jun;9(3):259-72. doi: 10.1007/BF01753729.
In order to study differences in antigen expression related to the different stages of the process of metastasis of human melanoma cell lines, we determined the expression pattern of a series of well-characterized genes in a set of human melanoma cell lines with different metastatic behavior in nude mice. This set included non-metastatic (IF6, 530), sporadically metastatic (M14, Mel 57), and frequently metastatic (BLM, MV3) cell lines after subcutaneous inoculation. To study the phenotype of these cell lines both the cultured cells and representative samples of local tumors at the inoculation site and their metastases in the lungs were immunostained with a panel of monoclonal antibodies directed against melanocytic differentiation or progression antigens. Although most cell lines (IF6, 530, M14 and Mel 57) showed HLA-DR expression in vitro, these antigens were lacking in all xenografted lesions studied with exception of the 530 cell line. 530 Xenografts, however, showed a dramatic down-regulation of HLA-DR compared with the cell line in vitro. The same phenomenon was seen with respect to ICAM-1 expression. The expression of all other antigens studied in xenografts, both in subcutaneous tumors and in lung lesions, was in general comparable to that in the melanoma cell lines in vitro, with exception of the 530 cell line. In all melanoma cell lines except 530 the degree of intra- and interlesional heterogeneity regarding the expression of all antigens studied was limited. Remarkably, comparison of the immunophenotype of the frequently metastasizing (BLM, MV3) and the sporadically (M14, Mel 57) or non-metastasizing (IF6, 530) cell lines showed that the two frequently metastasizing cell lines had marked expression of the progression antigens VLA-2 and epidermal growth factor receptor, and lack of expression of the differentiation antigen NKI-beteb. These findings warrant further studies on the role of these antigens in the process of metastasis of human melanoma cells in nude mice.
为了研究与人类黑色素瘤细胞系转移过程不同阶段相关的抗原表达差异，我们在一组在裸鼠中具有不同转移行为的人类黑色素瘤细胞系中，确定了一系列特征明确的基因的表达模式。该组包括皮下接种后非转移性（IF6、530）、偶发性转移性（M14、Mel 57）和频繁转移性（BLM、MV3）细胞系。为了研究这些细胞系的表型，对接种部位的局部肿瘤及其肺部转移灶的培养细胞和代表性样本，用一组针对黑素细胞分化或进展抗原的单克隆抗体进行免疫染色。尽管大多数细胞系（IF6、530、M14和Mel 57）在体外显示HLA-DR表达，但除530细胞系外，在所有研究的异种移植病变中均缺乏这些抗原。然而，与体外细胞系相比，530异种移植显示HLA-DR显著下调。ICAM-1表达也出现同样的现象。除530细胞系外，在异种移植中研究的所有其他抗原在皮下肿瘤和肺部病变中的表达，总体上与体外黑色素瘤细胞系中的表达相当。在除530以外的所有黑色素瘤细胞系中，所研究的所有抗原表达的瘤内和瘤间异质性程度有限。值得注意的是，对频繁转移（BLM、MV3）和偶发（M14、Mel 57）或非转移（IF6、530）细胞系的免疫表型进行比较发现，两个频繁转移的细胞系具有进展抗原VLA-2和表皮生长因子受体的显著表达，而缺乏分化抗原NKI-beteb的表达。这些发现值得进一步研究这些抗原在裸鼠中人类黑色素瘤细胞转移过程中的作用。
