Galectin-7 in lymphoma:: Elevated expression in human lymphoid malignancies and decreased lymphoma dissemination by antisense strategies in experimental model

Galectin-7 in lymphoma:: Elevated expression in human lymphoid malignancies and decreased lymphoma dissemination by antisense strategies in experimental model
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DOI:
10.1158/0008-5472.can-06-3891
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发表时间:
2007-03-15
期刊:
影响因子:
11.2
通讯作者:
St-Pierre, Yves
St-Pierre, Yves
中科院分区:
医学1区
文献类型:
--
作者:
Demers, Melanie;Biron-Pain, Katherine;St-Pierre, Yves

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半乳糖凝集素-7主要存在于复层鳞状上皮以及各种其他类型的癌细胞中。与半乳糖凝集素家族的其他成员一样,半乳糖凝集素-7的表达已显示出负调节一些肿瘤的发展,同时与其他肿瘤类型的进展相关。例如,半乳糖凝集素-7的上调与大鼠乳腺癌和T细胞恶性肿瘤的进展有关。在这里,我们提供的证据表明,半乳糖凝集素-7功能作为一个重要的分子在体内淋巴瘤细胞的传播。我们发现,用编码反义半乳糖凝集素-7 cDNA的质粒稳定转染淋巴瘤细胞显著抑制淋巴瘤细胞向外周器官的扩散和侵袭,从而增加小鼠的存活率。我们还发现,在侵袭性淋巴瘤细胞中半乳糖凝集素-7的抑制与肿瘤细胞在靶器官中的侵袭减少和基质金属蛋白酶-9(一种与非霍奇金淋巴瘤的不良预后相关的基因)的表达减少相关。我们最后检查了50个不同成熟B细胞肿瘤标本中半乳糖凝集素-7的表达,发现在相当大比例的成熟B细胞肿瘤中半乳糖凝集素-7表达水平高,但在正常B细胞中没有。总之,这些发现表明,半乳糖凝集素-7是一个潜在的治疗淋巴恶性肿瘤的治疗目标。
Galectin-7 is found mainly in stratified squamous epithelia as well as in various other types of cancer cells. As with other members of the galectin family, the expression of galectin-7 has been shown to negatively regulate the development of some tumors while correlating with the progression of other tumor types. For example, up-regulation of galectin-7 is associated with rat mammary carcinomas and with progression to T-cell malignancy. Here, we provide evidence indicating that galectin-7 functions as an important molecule in the dissemination of lymphoma cells in vivo. We found that stable transfection of lymphoma cells with a plasmid encoding antisense galectin-7 cDNA significantly inhibited the dissemination and invasion of lymphoma cells to peripheral organs, thereby increasing the survival of mice. We also found that inhibition of galectin-7 in aggressive lymphoma cells correlated with a decreased invasion of tumor cells in target organs and a reduced expression of matrix metalloproteinase-9, a gene associated with a poor prognosis in non-Hodgkin's lymphoma. We finally examined the expression of galectin-7 in 50 specimens of different mature B-cell neoplasms and found high galectin-7 expression levels in a significant proportion of mature B-cell neoplasms but not in normal B cells. Taken together, these findings suggest that galectin-7 is a potential therapeutic target in the treatment of lymphoid malignancies.