Demers Mélanie, Biron-Pain Katherine, Hébert Josée, Lamarre Alain, Magnaldo Thierry, St-Pierre Yves
INRS-Institut Armand-Frappier, University of Québec, Laval, Québec, Canada.
Cancer Res. 2007 Mar 15;67(6):2824-9. doi: 10.1158/0008-5472.CAN-06-3891.
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.
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的表达已被证明对某些肿瘤的发展具有负调控作用,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以及T细胞恶性肿瘤的进展有关。在此,我们提供证据表明半乳糖凝集素-7在淋巴瘤细胞体内播散中起重要作用。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可显著抑制淋巴瘤细胞向周围器官的播散和侵袭,从而提高小鼠的存活率。我们还发现,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以及基质金属蛋白酶-9的表达降低相关,基质金属蛋白酶-9是一种与非霍奇金淋巴瘤预后不良相关的基因。我们最后检测了50例不同成熟B细胞肿瘤标本中半乳糖凝集素-7的表达,发现相当一部分成熟B细胞肿瘤中半乳糖凝集素-7表达水平较高,而正常B细胞中则未检测到。综上所述,这些发现表明半乳糖凝集素-7是治疗淋巴恶性肿瘤的潜在治疗靶点。