Decidual NK cell-derived conditioned medium enhances capillary tube and network organization in an extravillous cytotrophoblast cell line

作者：Hu Y; Eastabrook G; Tan R; MacCalman C D; Dutz J P; von Dadelszen P^*

来源：Placenta, 2010, 31(3): 213-221.

DOI：10.1016/j.placenta.2009.12.011

• Decidual natural killer cells
• Extravillous cytotrophoblast
• Angiogenesis
• Capillary tube and network formation
• VEGF and ICAM-1

Extravillous cytotrophoblast (EVF) migration. invasion and endovascular differentiation are regulated by a variety of growth factors. cytokines and adhesion molecules. Decidual natural killer cells (dNK and their secreted cytokines probably modulate these processes In this study, we used dNK-derived conditioned medium (dNK-CM) to investigate whether or not (i) dNK-CM was able to enhance capillary tube and network formation of an EVT cell line, HTR8/SVneo, on Matrigel, (ii) PI3K/AKT pathway and p38 MAPK pathway activation were involved, and (iii) HTR8/SVneo surface ICAM-1 played a role. In the process of HTR8/SVneo endovascular differentiation. The results demonstrated that HTR8/SVneo constitutively form 'vascular' tubes and networks after culture on Matrigel. dNK-CM enhanced and maintained tube and network formation. acquiring an endothelium-like angiogenic morphology followed by increased VEGF-C production HTR8/SVneo cell expression level of VE-cadherin, PECAM-1, VCAM-1 and alpha nu beta 3 was unaltered by dNK-CM, whereas ICAM-1 expression level was increased Anti-human ICAM-1 blocking antibody inhibited HTR8/SVneo migration and partially reversed dNK-CM-mediated enhancement of HTR8/SVneo tube and network formation PI3K/AKT and p38 MAPK pathways were activated in dNK-CM-mediated enhancement of HTR8/SVneo tube and network formation The PI3K/AKT and p38 MAPK pathway inhibitors (LY294002 and SB202190, respectively) decreased dNK-CM-stimulated ICAM-1 induction, HTR8/SVneo migration, and reversed tube and network formation The results suggest that dNK cell-secreted growth factors and cytokines participate in the regulation of HTR8/SVneo endothelium-like tube formation Adhesion molecules, particularly ICAM-1, expressed on EVT may participate in the process To our knowledge, this is the first report of a role for ICAM-1 in EVT angiogenesis, as previously reported for endothelial cells.

• 出版日期2010-3