Human endometrial stromal cell-trophoblast interactions: mutual stimulation of chemotactic migration and promigratory roles of cell surface molecules CD82 and CEACAM1.
We have previously shown that the presence of trophoblast cells enhances invasiveness of decidualizing human endometrial stromal cells. The metastasis suppressor CD82, which has antimigratory function in tumor cells, is up-regulated in decidualizing endometrial stromal cells. CEACAM1 is expressed in trophoblast cells at the invasion front in early placenta and is considered proinvasive. Here, we investigate the role of CD82 and CEACAM1 in cocultures of the endometrial stromal cell line T-HESC and AC-1M88 trophoblast cells. In transwell migration assays, chemotaxis of AC-1M88 cells was stimulated by coplated T-HESC in the lower compartment or by the combination of heparin-binding EGF-like growth factor (HB-EGF), interleukin-1 beta (IL-1beta), and leukemia inhibitory factor (LIF), local factors present at the time of implantation. In an implantation model of AC-1M88 trophoblast spheroids on a monolayer of T-HESC, spheroid expansion was enhanced in the presence of HB-EGF/IL-1beta/LIF. Silencing of CEACAM1 in AC-1M88 blunted this response. Chemotactic migration of T-HESC was stimulated by trophoblast secretions or HB-EGF/IL-1beta/LIF. These responses were suppressed by CD82 depletion in T-HESC. Proteome profiling revealed the presence of platelet-derived growth factor (PDGF)-AA in trophoblast supernatant. Chemotaxis of T-HESC toward PDGF-AA was significantly inhibited by CD82 silencing. Neutralization of PDGF-AA in AC-1M88 conditioned media reduced the chemotactic effect on T-HESC. In summary, we demonstrate a mutual stimulation of chemotactic migration between trophoblast and endometrial stromal cells and promigratory roles for the cell surface molecules CEACAM1 and CD82, which may serve to support tissue remodeling at the implantation site.
Endokrinologikum Hamburg, Hamburg, Germany. gellersen@endokrinologikum.com
Birgit
B
Gellersen
Anja
A
Wolf
Michelle
M
Kruse
Maren
M
Schwenke
Ana-Maria
AM
Bamberger
D015703:Antigens, CD / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002450:Cell Communication; D002460:Cell Line; D002465:Cell Movement; D002633:Chemotaxis; D018920:Coculture Techniques; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D051861:Kangai-1 Protein / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020543:Proteome / Q000378:metabolism; D018874:Spheroids, Cellular / Q000502:physiology; D017154:Stromal Cells / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism*
D015703:Antigens, CD; C069847:CD66 antigens; C497688:CD82 protein, human; D015815:Cell Adhesion Molecules; D051861:Kangai-1 Protein; D010982:Platelet-Derived Growth Factor; D020543:Proteome; C075278:platelet-derived growth factor A; C512478:EGFR protein, human; D066246:ErbB Receptors