TGF-β isoforms induce EMT independent migration of ovarian cancer cells.
TGF-β isoforms induce EMT independent migration of ovarian cancer cells.
复制标题
DOI：
10.1186/s12935-014-0072-1
复制
发表时间：
2014
影响因子：
5.8
通讯作者：
Sundfeldt K
中科院分区：
文献类型：
--
作者：
Gao J;Zhu Y;Nilsson M;Sundfeldt K
转化生长因子-β(TGFR-β)通过调节细胞生长、上皮向间充质转化、迁移/侵袭和转移，在肿瘤发生发展中发挥重要作用。上皮性标记物E-钙粘素、claudin-3和claudin-4在人类腺癌中普遍降低，实际上在卵巢癌发生过程中上调。在人卵巢癌中，转化生长因子-β1可以抑制或促进肿瘤进展，但其他转化生长因子-β亚型(转化生长因子-β2和转化生长因子-β3)是否具有类似的作用尚不清楚。在这项研究中，我们通过BrdU标记、划痕损伤和跨滤膜迁移实验，研究了转化生长因子-β亚型(转化生长因子-β1-3)在人浆液性腺癌NIH-OVCAR3细胞系中诱导增殖和迁移的能力。测定跨上皮阻力，光镜下观察EMT。用qRT-PCR和免疫印迹法检测黏附因子、紧密连接因子和EMT相关转录因子的表达。所有转化生长因子-β亚型均呈剂量依赖性抑制NIHOVCAR3细胞生长，刺激肿瘤细胞迁移，其作用相似。诱导间充质标志物N-钙粘蛋白和claudin-1的表达，下调阻滞素的表达。然而，迁移细胞保持上皮形态和E-钙粘附素的表达。单独使用转化生长因子-ZEB1-3处理后，E-钙粘素抑制因子蜗牛的基因表达水平仍然较低，而β的表达增强。转化生长因子-β-1、转化生长因子-β-2和转化生长因子-β-3促进卵巢癌细胞的迁移，不依赖于细胞增殖，也不会转化为完全的EMT表型。卵巢上皮癌通常转移到周围组织或腹膜内，而不是侵犯血管设定距离转移。我们的结果提出了一个问题，卵巢癌主要是通过集体迁移传播，而不是通过单个细胞侵袭传播。
Transforming growth factor beta (TGF-β) plays major roles in tumorigenesis by regulating cell growth, epithelial-to-mesenchymal transition (EMT), migration/invasion and metastasis. The epithelial markers E-cadherin, claudin-3 and claudin-4, commonly decreased in human adenocarcinomas are actually up regulated during ovarian carcinogenesis. In human ovarian cancer TGF-β1 may either suppress or promote tumor progression, but whether other TGF-β isoforms (TGF-β2 and TGF-β3) exert similar effects is not known. In this study we investigated the ability of the TGF-β isoforms (TGF-β1-3) to induce proliferation and migration by BrdU labeling, scratch wound and trans-filter migration assays in the human serous adenocarcinoma cell-line NIH-OVCAR3. Transepithelial resistance was measured and EMT observed by light-microscopy. Expression of adherens-, tight-junction and EMT-related transcription factors was analyzed by qRT-PCR and immunoblotting. All TGF-β isoforms dose-dependently inhibited NIH-OVCAR3 cell growth, stimulated tumor cell migration with similar efficiency. The mesenchymal marker N-cadherin and claudin-1 expression was induced and occludin down regulated. However, migrating cells retained an epithelial shape and E-cadherin expression. The E-cadherin repressor SNAIL mRNA levels remained low independently of TGF-β1-3 treatment while ZEB1 expression was enhanced. TGF-β1, TGF-β2 and TGF-β3 promote migration of NIH-OVCAR3 ovarian cancer cells independently of cell proliferation and without conversion to a complete EMT phenotype. Epithelial ovarian cancer commonly metastasis to the surrounding tissue or inside the peritoneum rather than invading blood vessels to set distance metastasis. Our result raises the question whether ovarian cancer primarily spread via collective migration than via single cell invasion.
登录
查看更多内容
影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
4.7
作者：
Rodriguez, GC;Haisley, C;Stack, MS
通讯作者：
Stack, MS
DOI：
10.1097/pgp.0b013e31820d20ba
发表时间：
2011-07-01
影响因子：
2.4
作者：
Koebel, Martin;Turbin, Dmitry;Gilks, C. Blake
通讯作者：
Gilks, C. Blake
影响因子：
8
作者：
Macpherson, I. R.;Hooper, S.;Brunton, V. G.
通讯作者：
Brunton, V. G.
Claudin-1上调阻遏物ZEB-1以抑制结肠癌细胞中的E-钙粘蛋白表达。
影响因子：
29.4
作者：
Singh AB;Sharma A;Smith JJ;Krishnan M;Chen X;Eschrich S;Washington MK;Yeatman TJ;Beauchamp RD;Dhawan P
通讯作者：
Dhawan P