Placenta
Volume 31, Issue 3 , Pages 213-221, March 2010

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

  • Y. Hu

      Affiliations

    • Department of Obstetrics and Gynaecology, University of British Columbia, 2H30-4500 Oak Street, Vancouver, BC V6H 3N1, Canada
    • The Child and Family Research Institute, University of British Columbia, 950 28th Avenue, Vancouver, BC V5Z 4H4, Canada
    • ,
  • G. Eastabrook

      Affiliations

    • Department of Obstetrics and Gynaecology, University of British Columbia, 2H30-4500 Oak Street, Vancouver, BC V6H 3N1, Canada
    • The Child and Family Research Institute, University of British Columbia, 950 28th Avenue, Vancouver, BC V5Z 4H4, Canada
    • ,
  • R. Tan

      Affiliations

    • Department of Pathology and Laboratory Medicine, University of British Columbia, 950 28th Avenue, Vancouver, BC V5Z 4H4, Canada
    • The Child and Family Research Institute, University of British Columbia, 950 28th Avenue, Vancouver, BC V5Z 4H4, Canada
    • ,
  • C.D. MacCalman

      Affiliations

    • Department of Obstetrics and Gynaecology, University of British Columbia, 2H30-4500 Oak Street, Vancouver, BC V6H 3N1, Canada
    • The Child and Family Research Institute, University of British Columbia, 950 28th Avenue, Vancouver, BC V5Z 4H4, Canada
    • ,
  • J.P. Dutz

      Affiliations

    • Department of Dermatology and Skin Science, University of British Columbia, 950 28th Avenue, Vancouver, BC V5Z 4H4, Canada
    • The Child and Family Research Institute, University of British Columbia, 950 28th Avenue, Vancouver, BC V5Z 4H4, Canada
    • ,
  • P. von Dadelszen

      Affiliations

    • Department of Obstetrics and Gynaecology, University of British Columbia, 2H30-4500 Oak Street, Vancouver, BC V6H 3N1, Canada
    • The Child and Family Research Institute, University of British Columbia, 950 28th Avenue, Vancouver, BC V5Z 4H4, Canada
    • Corresponding Author InformationCorrespondence to: P. von Dadelszen, Department of Obstetrics and Gynaecology, University of British Columbia, 2H30-4500 Oak Street, Vancouver, BC V6H 3N1, Canada. Tel.: +1 604 875 3054; fax: +1 604 875 2725.

Accepted 10 December 2009. published online 18 January 2010.

Abstract 

Extravillous cytotrophoblast (EVT) 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 αvβ3 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.

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

Abbreviations: dNK cells, decidual natural killer cells, EVT, extravillous cytotrophoblast, dNK-CM, dNK-derived conditioned medium, CTB, cytotrophoblast

 

☆ The study was funded by a pilot grant from the Infection and Immunity Program, Child and Family Research Institute (CFRI). YH is funded through grants from the Canadian Institutes for Health Research, from whom PvD receives salary support. CDMacC and PvD receive salary support from CFRI. PvD, JPD, and RT receive salary support from the Michael Smith Foundation for Health Research.

PII: S0143-4004(09)00401-9

doi:10.1016/j.placenta.2009.12.011

Placenta
Volume 31, Issue 3 , Pages 213-221, March 2010

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