Annabi Bayader, Zgheib Alain, Annabi Borhane
Laboratoire d'Oncologie Moléculaire, Département de Chimie, Centre de recherche BIOMED, Université du Québec à Montréal, Quebec, Canada.
Département de Physiologie Moléculaire et Intégrative, Faculté de Médecine, Université de Montréal, Montreal, Canada.
Int J Stem Cells. 2017 May 30;10(1):103-113. doi: 10.15283/ijsc16032.
Tumour necrosis factor (TNF)- activation of mesenchymal stromal cells (MSC) enhances their tumour-suppressive properties and tumour-homing ability. The molecular actors involved are unknown. We found that TNF induced MSC migration and tubulogenesis which correlated with a dose-dependent increase in -1 and -3 transcript levels. TNF triggered cyclooxygenase (COX)-2 expression, whereas specific siRNA-mediated gene silencing of -2 resulted in an amplified COX-2 expression, tubulogenesis, and migratory response partially due to a rapid and sustained increase in NF-B phosphorylation status. Our results highlight a suppressive role for the caveolar component -2 in the angiogenic and inflammatory regulation of TNF-activated MSC.
肿瘤坏死因子(TNF)激活间充质基质细胞(MSC)可增强其肿瘤抑制特性和肿瘤归巢能力。其中涉及的分子机制尚不清楚。我们发现TNF诱导MSC迁移和管状结构形成,这与-1和-3转录水平的剂量依赖性增加相关。TNF触发环氧化酶(COX)-2表达,而特定的siRNA介导的-2基因沉默导致COX-2表达、管状结构形成和迁移反应增强,部分原因是NF-κB磷酸化状态迅速且持续增加。我们的结果突出了小窝成分-2在TNF激活的MSC血管生成和炎症调节中的抑制作用。