Institut National de la Santé et de la Recherche Medicale U643, Centre Hospitalier Universitaire de Nantes, Nantes, France.
J Histochem Cytochem. 2010 Jun;58(6):553-65. doi: 10.1369/jhc.2010.955237. Epub 2010 Mar 2.
Galectin-3 (Gal-3) is a multifunctional protein that plays different roles in cancer biology. To better understand the role of Gal-3 and its ligands during colon carcinogenesis, we studied its expression in tumors induced in rats treated with 1,2-dimethylhydrazine (DMH) and in human tissues. Normal colon from untreated rats showed no staining using two specific monoclonal antibodies. In contrast, morphologically normal colon from DMH-treated rats and dysplastic aberrant crypt foci were strongly stained, indicating that increased Gal-3 expression is an early event during the neoplastic transformation in colon cells. Gal-3 was weakly expressed in adenocarcinomas. Overall, the Gal-3 expression pattern observed in the DMH rat model closely resembles that displayed by human colon stained with the same antibodies. We also found that Gal-3 phosphorylation diminishes in serines while increasing in tyrosines during rat colon carcinogenesis. Finally, we showed that Gal-3-ligands expression is strikingly similar in rat and human malignant colon and in non-malignant tissues. In conclusion, the DMH-induced rat colon cancer model displays expression patterns of Gal-3 and its ligands very similar to those observed in human samples. This animal model should contribute to clarifying the role of Gal-3 in colon carcinogenesis and also to finding effective preventive cancer agents based on Gal-3 targeting.
半乳糖凝集素-3(Gal-3)是一种多功能蛋白,在癌症生物学中发挥着不同的作用。为了更好地了解 Gal-3 及其配体在结肠癌发生过程中的作用,我们研究了其在 1,2-二甲基肼(DMH)处理的大鼠诱导的肿瘤和人类组织中的表达。未经处理的大鼠的正常结肠使用两种特异性单克隆抗体未染色。相比之下,形态正常的 DMH 处理大鼠结肠和发育异常的异常隐窝灶强烈染色,表明 Gal-3 表达增加是结肠细胞发生肿瘤转化的早期事件。Gal-3 在腺癌中表达较弱。总体而言,在 DMH 大鼠模型中观察到的 Gal-3 表达模式与用相同抗体染色的人类结肠非常相似。我们还发现,Gal-3 在丝氨酸上的磷酸化减少,而在酪氨酸上的磷酸化增加,在大鼠结肠癌发生过程中。最后,我们表明 Gal-3-配体在大鼠和人类恶性结肠以及非恶性组织中的表达非常相似。总之,DMH 诱导的大鼠结肠癌模型显示出与在人类样本中观察到的 Gal-3 和其配体表达模式非常相似。这种动物模型应该有助于阐明 Gal-3 在结肠癌发生中的作用,并找到基于 Gal-3 靶向的有效预防癌症药物。