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Control of human endometrial stromal cell motility by PDGF-BB, HB-EGF and trophoblast-secreted factors

Control of human endometrial stromal cell motility by PDGF-BB, HB-EGF and trophoblast-secreted factors
Control of human endometrial stromal cell motility by PDGF-BB, HB-EGF and trophoblast-secreted factors
Human implantation involves extensive tissue remodeling at the fetal-maternal interface. It is becoming increasingly evident that not only trophoblast, but also decidualizing endometrial stromal cells are inherently motile and invasive, and likely contribute to the highly dynamic processes at the implantation site. The present study was undertaken to further characterize the mechanisms involved in the regulation of endometrial stromal cell motility and to identify trophoblast-derived factors that modulate migration. Among local growth factors known to be present at the time of implantation, heparin-binding epidermal growth factor-like growth factor (HB-EGF) triggered chemotaxis (directed locomotion), whereas platelet-derived growth factor (PDGF)-BB elicited both chemotaxis and chemokinesis (non-directed locomotion) of endometrial stromal cells. Supernatants of the trophoblast cell line AC-1M88 and of first trimester villous explant cultures stimulated chemotaxis but not chemokinesis. Proteome profiling for cytokines and angiogenesis factors revealed neither PDGF-BB nor HB-EGF in conditioned media from trophoblast cells or villous explants, while placental growth factor, vascular endothelial growth factor and PDGF-AA were identified as prominent secretory products. Among these, only PDGF-AA triggered endometrial stromal cell chemotaxis. Neutralization of PDGF-AA in trophoblast conditioned media, however, did not diminish chemoattractant activity, suggesting the presence of additional trophoblast-derived chemotactic factors. Pathway inhibitor studies revealed ERK1/2, PI3 kinase/Akt and p38 signaling as relevant for chemotactic motility, whereas chemokinesis depended primarily on PI3 kinase/Akt activation. Both chemotaxis and chemokinesis were stimulated upon inhibition of Rho-associated, coiled-coil containing protein kinase. The chemotactic response to trophoblast secretions was not blunted by inhibition of isolated signaling cascades, indicating activation of overlapping pathways in trophoblast-endometrial communication. In conclusion, trophoblast signals attract endometrial stromal cells, while PDGF-BB and HB-EGF, although not identified as trophoblast-derived, are local growth factors that may serve to fine-tune directed and non-directed migration at the implantation site.
1932-6203
e54336-[14pp]
Schwenke, M.
b1ecf9f1-0cd9-4b33-b302-54964feaec75
Knofler, M.
b88e21c2-db3c-47d3-b228-3c8c2769ddee
Velicky, P.
ff73317e-cd49-4932-b358-72dccaf07309
Weimar, C.H.
1436b5d4-adbe-416f-bd9c-9ea02ba6c6ad
Kruse, M.
88d22afb-9ec8-4a3d-affb-4cb19b8d2ecb
Samalecos, A.
61fb032d-d25f-44d7-909d-b6dd8f6059bf
Wolf, A.
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Macklon, N.S.
7db1f4fc-a9f6-431f-a1f2-297bb8c9fb7e
Bamberger, A.M.
ff5a55c2-624c-43f6-8fd8-b561f509fdd9
Gellersen, B.
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Schwenke, M.
b1ecf9f1-0cd9-4b33-b302-54964feaec75
Knofler, M.
b88e21c2-db3c-47d3-b228-3c8c2769ddee
Velicky, P.
ff73317e-cd49-4932-b358-72dccaf07309
Weimar, C.H.
1436b5d4-adbe-416f-bd9c-9ea02ba6c6ad
Kruse, M.
88d22afb-9ec8-4a3d-affb-4cb19b8d2ecb
Samalecos, A.
61fb032d-d25f-44d7-909d-b6dd8f6059bf
Wolf, A.
d282c455-b006-4706-b06e-f452cf495bbe
Macklon, N.S.
7db1f4fc-a9f6-431f-a1f2-297bb8c9fb7e
Bamberger, A.M.
ff5a55c2-624c-43f6-8fd8-b561f509fdd9
Gellersen, B.
0c40a571-5956-4d24-837a-19b1eff3d973

Schwenke, M., Knofler, M., Velicky, P., Weimar, C.H., Kruse, M., Samalecos, A., Wolf, A., Macklon, N.S., Bamberger, A.M. and Gellersen, B. (2013) Control of human endometrial stromal cell motility by PDGF-BB, HB-EGF and trophoblast-secreted factors. PLoS ONE, 8 (1), e54336-[14pp]. (doi:10.1371/journal.pone.0054336). (PMID:23349855)

Record type: Article

Abstract

Human implantation involves extensive tissue remodeling at the fetal-maternal interface. It is becoming increasingly evident that not only trophoblast, but also decidualizing endometrial stromal cells are inherently motile and invasive, and likely contribute to the highly dynamic processes at the implantation site. The present study was undertaken to further characterize the mechanisms involved in the regulation of endometrial stromal cell motility and to identify trophoblast-derived factors that modulate migration. Among local growth factors known to be present at the time of implantation, heparin-binding epidermal growth factor-like growth factor (HB-EGF) triggered chemotaxis (directed locomotion), whereas platelet-derived growth factor (PDGF)-BB elicited both chemotaxis and chemokinesis (non-directed locomotion) of endometrial stromal cells. Supernatants of the trophoblast cell line AC-1M88 and of first trimester villous explant cultures stimulated chemotaxis but not chemokinesis. Proteome profiling for cytokines and angiogenesis factors revealed neither PDGF-BB nor HB-EGF in conditioned media from trophoblast cells or villous explants, while placental growth factor, vascular endothelial growth factor and PDGF-AA were identified as prominent secretory products. Among these, only PDGF-AA triggered endometrial stromal cell chemotaxis. Neutralization of PDGF-AA in trophoblast conditioned media, however, did not diminish chemoattractant activity, suggesting the presence of additional trophoblast-derived chemotactic factors. Pathway inhibitor studies revealed ERK1/2, PI3 kinase/Akt and p38 signaling as relevant for chemotactic motility, whereas chemokinesis depended primarily on PI3 kinase/Akt activation. Both chemotaxis and chemokinesis were stimulated upon inhibition of Rho-associated, coiled-coil containing protein kinase. The chemotactic response to trophoblast secretions was not blunted by inhibition of isolated signaling cascades, indicating activation of overlapping pathways in trophoblast-endometrial communication. In conclusion, trophoblast signals attract endometrial stromal cells, while PDGF-BB and HB-EGF, although not identified as trophoblast-derived, are local growth factors that may serve to fine-tune directed and non-directed migration at the implantation site.

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e-pub ahead of print date: 21 January 2013
Organisations: Human Development & Health

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Local EPrints ID: 347983
URI: http://eprints.soton.ac.uk/id/eprint/347983
ISSN: 1932-6203
PURE UUID: dab7a00e-c175-41b0-8e88-f91288c32d7d

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Date deposited: 05 Feb 2013 12:17
Last modified: 27 Oct 2023 01:42

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Contributors

Author: M. Schwenke
Author: M. Knofler
Author: P. Velicky
Author: C.H. Weimar
Author: M. Kruse
Author: A. Samalecos
Author: A. Wolf
Author: N.S. Macklon
Author: A.M. Bamberger
Author: B. Gellersen

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