PDF(Pubmed)
Abstract：
Leptin is an obesity-related hormone that plays an important role in breast cancer progression. Vasculogenic mimicry (VM) refers to the formation of vascular channels lined by tumor cells. This study aimed to investigate the relationship between leptin and VM in human breast cancer cells. VM was measured by a 3D culture assay. Signal transducers and activators of transcription 3 (STAT3) signaling, aquaporin-1 (AQP1), and the expression of VM-related proteins, including vascular endothelial cadherin (VE-cadherin), twist, matrix metalloproteinase-2 (MMP-2), and laminin subunit 5 gamma-2 (LAMC2), were examined by Western blot. AQP1 mRNA was analyzed by a reverse transcriptase-polymerase chain reaction (RT-PCR). Leptin increased VM and upregulated phospho-STAT3, VE-cadherin, twist, MMP-2, and LAMC2. These effects were inhibited by the leptin receptor-blocking peptide, Ob-R BP, and the STAT3 inhibitor, AG490. A positive correlation between leptin and AQP1 mRNA was observed and was confirmed by RT-PCR. Leptin upregulated AQP1 expression, which was blocked by Ob-R BP and AG490. AQP1 overexpression increased VM and the expression of VM-related proteins. AQP1 silencing inhibited leptin-induced VM and the expression of VM-related proteins. Thus, these results showed that leptin facilitates VM in breast cancer cells via the Ob-R/STAT3 pathway and that AQP1 is a key mediator in leptin-induced VM.
摘要：
瘦素是一种肥胖相关激素，在乳腺癌进展中起重要作用。血管生成拟态(VM)是指由肿瘤细胞排列的血管通道的形成。本研究旨在探讨人乳腺癌细胞中瘦素与VM的关系。通过3D培养测定来测量VM。信号转导和转录激活因子3（STAT3）信号，水通道蛋白-1（AQP1），和VM相关蛋白的表达，包括血管内皮钙粘蛋白（VE-cadherin），twist,基质金属蛋白酶-2(MMP-2),和层粘连蛋白亚基5γ-2（LAMC2），通过蛋白质印迹检查。通过逆转录酶-聚合酶链反应（RT-PCR）分析AQP1mRNA。瘦素增加VM并上调磷酸-STAT3，VE-钙黏着蛋白，twist,MMP-2和LAMC2。这些作用被瘦素受体阻断肽抑制，Ob-RBP，和STAT3抑制剂，AG490.观察到瘦素与AQP1mRNA呈正相关，并通过RT-PCR证实。瘦素上调AQP1表达,被Ob-RBP和AG490阻断。AQP1过表达增加VM和VM相关蛋白的表达。AQP1沉默抑制瘦素诱导的VM和VM相关蛋白的表达。因此，这些结果表明,瘦素通过Ob-R/STAT3途径促进乳腺癌细胞中的VM,而AQP1是瘦素诱导的VM的关键介质.
