Suppression of tumor growth by galectin-7 gene transfer
Suppression of tumor growth by galectin-7 gene transfer
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DOI：
10.1158/0008-5472.can-04-0985
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发表时间：
2004-08-15
期刊：
影响因子：
11.2
通讯作者：
Liu, FT
中科院分区：
文献类型：
--
作者：
Ueda, S;Kuwabara, I;Liu, FT
Galectin-7是一种β-半乳糖苷结合的动物凝集素，在复层上皮细胞中特异表达。其表达受P53的诱导，在鳞癌中表达下调。其他研究人员此前发现Galectin-7是一种促凋亡蛋白，我们发现Galectin-7在HeLa细胞中的异位表达使细胞对各种凋亡刺激更加敏感。在本研究中，我们发现Galectin-7在人结肠癌细胞系DLD-1中的异位表达也使该细胞在不同条件下对凋亡更加敏感。我们还发现，在正常培养条件下，在没有细胞凋亡的情况下，Galectin-7转基因的DLD-1(DLD-1-Gal7)细胞的生长速度明显慢于对照组(DLD-1-V)。此外，在非锚定细胞生长条件下，DLD-1-Gal7细胞形成的集落数量明显少于DLD-1-V细胞。最重要的是，接种S.C.的DLD-1-Gal7细胞与DLD-1-V细胞相比，肿瘤形成显著减少。变成严重的联合免疫缺陷小鼠。体内5-溴-2‘-脱氧尿嘧啶核苷掺入实验表明，DLD-1-Gal7肿瘤的增殖率明显低于DLD-1-V肿瘤。DLD-1-Gal7肿瘤的血管密度也低于DLD-1-V肿瘤，提示Galectin-7的异位表达抑制了血管生成。这可能是Galectin-7在体内对肿瘤生长的抑制作用强于体外的部分原因。我们的结果表明Galectin-7具有抑制肿瘤生长的作用，提示Galectin-7基因转移或其他特异性诱导Galectin-7表达的方法可能是一种新的癌症治疗方法。
Galectin-7 is a beta-galactoside-binding animal lectin specifically expressed in stratified epithelia. Its expression is inducible by p53 and is down-regulated in squamous cell carcinomas. Other investigators previously showed that galectin-7 is a proapoptotic protein, and we showed that ectopic expression of galectin-7 in HeLa cells renders the cells more sensitive to a variety of apoptotic stimuli. In the present study, we showed that ectopic expression of galectin-7 in the human colon carcinoma cell line DLD-1 also made the cells more sensitive to apoptosis under various conditions. We also found that galectin-7-transfected DLD-1 (DLD-1-Gal7) cells grew significantly more slowly than control transfectants (DLD-1-V) under normal culture conditions in the absence of apoptosis. Moreover, a significantly lower number of colonies were formed from DLD-1-Gal7 cells than from DLD-1-V cells under anchorage-independent cell growth conditions. Most importantly, tumor formation from DLD-1-Gal7 cells was dramatically reduced compared with DLD-1-V cells when these cells were inoculated s.c. into severe combined immunodeficient mice. DLD-1-Gal7 tumors showed a significantly lower proliferation rate than DLD-1-V tumors as determined by in vivo 5-bromo-2'-deoxyuridine incorporation. DLD-1-Gal7 tumors also contained a lower density of blood vessels than DLD-1-V tumors, suggesting that ectopic expression of galectin-7 suppresses angiogenesis. This may partially account for the greater suppressive effect of galectin-7 on tumor growth in vivo than in vitro. Our results show that galectin-7 has a suppressive effect on tumor growth, suggesting that galectin-7 gene transfer or other means of specifically inducing galectin-7 expression may be a new approach for management of cancers.