Moisan S, Demers M, Mercier J, Magnaldo T, Potworowski E F, St-Pierre Y
INRS-Institut Armand-Frappier, University of uébec, Laval, Canada.
Leukemia. 2003 Apr;17(4):751-9. doi: 10.1038/sj.leu.2402870.
We have previously shown that ICAM-1-deficient mice were resistant to lymphoma dissemination of intravenously injected 164T2 lymphoma cells. Highly aggressive variants of this cell line, however, could overcome this resistance. To discern the complex pattern of gene expression involved in the evolution of aggressiveness in lymphoma cells, we compared the transcriptome of 164T2 cells with that of their aggressive variants using cDNA arrays. We identified several genes that were differentially expressed in nonmetastatic lymphoma cells and their metastatic variants. Galectin-7, associated with the development of chemically induced mammary carcinoma, was one such gene whose expression was significantly upregulated. We showed that it was constitutively expressed in aggressive variants, at both mRNA and protein levels. Galectin-7 expression in aggressive lymphoma cells was induced upon in vivo selection in several organs, including the thymus, the spleen and kidneys. We also showed that treatment of nonaggressive lymphoma cells with 5-aza-2'-deoxycytidine was sufficient to induce galectin-7 gene expression. This report is the first to show that galectin-7 is expressed in aggressive lymphoma.
我们之前已经表明,ICAM-1缺陷型小鼠对静脉注射的164T2淋巴瘤细胞的淋巴瘤扩散具有抗性。然而,该细胞系的高侵袭性变体能够克服这种抗性。为了辨别淋巴瘤细胞侵袭性进化过程中涉及的复杂基因表达模式,我们使用cDNA阵列比较了164T2细胞与其侵袭性变体的转录组。我们鉴定出了几个在非转移性淋巴瘤细胞及其转移性变体中差异表达的基因。与化学诱导的乳腺癌发生相关的半乳糖凝集素-7就是这样一个表达显著上调的基因。我们表明,它在侵袭性变体中以mRNA和蛋白质水平组成性表达。在包括胸腺、脾脏和肾脏在内的多个器官中进行体内选择后,侵袭性淋巴瘤细胞中的半乳糖凝集素-7表达被诱导。我们还表明,用5-氮杂-2'-脱氧胞苷处理非侵袭性淋巴瘤细胞足以诱导半乳糖凝集素-7基因表达。本报告首次表明半乳糖凝集素-7在侵袭性淋巴瘤中表达。