Hypoxia Up-Regulates Galectin-3 in Mammary Tumor Progression and Metastasis.
Hypoxia Up-Regulates Galectin-3 in Mammary Tumor Progression and Metastasis.
复制标题
DOI：
10.1371/journal.pone.0134458
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Gärtner F
中科院分区：
文献类型：
--
作者：
de Oliveira JT;Ribeiro C;Barros R;Gomes C;de Matos AJ;Reis CA;Rutteman GR;Gärtner F
肿瘤微环境包括癌细胞的几种应激条件，如缺氧、氧化应激和pH值改变。半乳糖凝集素-3是β-半乳糖苷结合动物凝集素家族的一个被充分研究的成员，它与转移的多个步骤有关，如细胞-细胞和细胞-ECM粘附、促进血管生成、细胞增殖和抗凋亡。然而，在几种类型的癌症中观察到其异常的上调和下调表达。因此，调节肿瘤环境中半乳糖凝集素-3表达的机制尚不清楚。为了证明缺氧在调节犬乳腺肿瘤（CMT）中半乳糖凝集素-3表达中的假定作用，进行了体外和体内研究。在恶性CMT细胞中，观察到缺氧诱导半乳糖凝集素-3的表达，这种现象几乎完全被CMT-U27细胞的过氧化氢酶处理所阻止。在mRNA水平证实了半乳糖凝集素-3表达的增加。在缺氧条件下，半乳糖凝集素-3的表达从主要的核位置转移到细胞质和膜表达。在体内研究中，半乳糖凝集素-3在原发性肿瘤和已确定的转移瘤的缺氧区域中过表达。因此，肿瘤缺氧上调半乳糖凝集素-3的表达，这反过来可能增加肿瘤的侵袭性。
The tumor microenvironment encompasses several stressful conditions for cancer cells such as hypoxia, oxidative stress and pH alterations. Galectin-3, a well-studied member of the beta-galactoside-binding animal family of lectins has been implicated in multiple steps of metastasis as cell-cell and cell-ECM adhesion, promotion of angiogenesis, cell proliferation and resistance to apoptosis. However, both its aberrantly up- and down-regulated expression was observed in several types of cancer. Thus, the mechanisms that regulate galectin-3 expression in neoplastic settings are not clear. In order to demonstrate the putative role of hypoxia in regulating galectin-3 expression in canine mammary tumors (CMT), in vitro and in vivo studies were performed. In malignant CMT cells, hypoxia was observed to induce expression of galectin-3, a phenomenon that was almost completely prevented by catalase treatment of CMT-U27 cells. Increased galectin-3 expression was confirmed at the mRNA level. Under hypoxic conditions the expression of galectin-3 shifts from a predominant nuclear location to cytoplasmic and membrane expressions. In in vivo studies, galectin-3 was overexpressed in hypoxic areas of primary tumors and well-established metastases. Tumor hypoxia thus up-regulates the expression of galectin-3, which may in turn increase tumor aggressiveness.