Demers Mélanie, Magnaldo Thierry, St-Pierre Yves
INRS-Institut Armand-Frappier, University of Québec, Laval, Québec, Canada.
Cancer Res. 2005 Jun 15;65(12):5205-10. doi: 10.1158/0008-5472.CAN-05-0134.
Metastasis is a multistep process by which cancer cells, after acquiring several capabilities, spread to distinct sites in the body. It is the major cause of death in individuals suffering from cancer. We have recently identified galectin-7 as a new gene associated with the progression of T cell lymphoma toward a metastatic phenotype, suggesting a possible causal relationship. The present study was designed to investigate the role of galectin-7 in lymphoma. We found that the development of thymic lymphoma was accelerated when induced by lymphoma cells overexpressing galectin-7. Moreover, transfection of an expression vector containing the galectin-7 gene in low metastatic lymphoma cells increased their metastatic behavior and confers these cells with the new ability to overcome the resistance of intercellular adhesion molecule-1-deficient mice to lymphoma dissemination. Finally, we provide data suggesting that galectin-7 modulates the aggressive behavior of lymphoma cells by controlling the expression of metastatic genes, such as MMP-9. This hypothesis is based on the following evidence: (a) galectin-7 transfectants have higher levels of MMP-9 expression, (b) addition of beta-lactose completely inhibits expression of MMP-9 by galectin-7 transfectants, and (c) recombinant forms of galectin-7 induces the expression of MMP-9 in both mouse and human lymphoma cells. Our results have uncovered the existence of a previously undescribed activity, the promotion of cancer cell malignancy, to galectin-7.
转移是一个多步骤过程，在此过程中癌细胞在获得多种能力后扩散至身体的不同部位。它是癌症患者死亡的主要原因。我们最近鉴定出半乳糖凝集素-7是一个与T细胞淋巴瘤向转移表型进展相关的新基因，提示了一种可能的因果关系。本研究旨在探讨半乳糖凝集素-7在淋巴瘤中的作用。我们发现，当由过表达半乳糖凝集素-7的淋巴瘤细胞诱导时，胸腺淋巴瘤的发展加速。此外，在低转移性淋巴瘤细胞中转染含有半乳糖凝集素-7基因的表达载体可增加其转移行为，并赋予这些细胞克服细胞间黏附分子-1缺陷小鼠对淋巴瘤扩散抗性的新能力。最后，我们提供的数据表明，半乳糖凝集素-7通过控制诸如基质金属蛋白酶-9等转移基因的表达来调节淋巴瘤细胞的侵袭行为。这一假设基于以下证据：(a) 半乳糖凝集素-7转染细胞具有更高水平的基质金属蛋白酶-9表达；(b) 添加β-乳糖可完全抑制半乳糖凝集素-7转染细胞中基质金属蛋白酶-9的表达；(c) 重组形式的半乳糖凝集素-7可诱导小鼠和人淋巴瘤细胞中基质金属蛋白酶-9的表达。我们研究结果揭示了半乳糖凝集素-7存在一种以前未描述的活性，即促进癌细胞恶性化。
