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Inhibition of trophoblast cell invasion by TGFB1, 2, and 3 is associated with a decrease in active proteases

Lookup NU author(s): Dr Gendie Lash, Dr Harry Otun, Barbara Innes, Dr Judith Bulmer, Dr Roger Searle, Professor Steve Robson

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Abstract

Invasion of extravillous trophoblast cells into the uterus in human pregnancy is tightly regulated. The transforming growth factor-beta (TGFB) family has been suggested to play a role in controlling this process. We hypothesized that TGFB1, 2, and 3 would inhibit the invasive capacity of extravillous trophoblast cells. We also studied trophoblast apoptosis and proliferation and secreted protease levels as potential mechanisms by which these cytokines may act. Inhibition of endogenous TGFB1, 2, and 3 with neutralizing antibodies increased the invasive capacity of extravillous trophoblast cells derived from placental explants. Similarly, addition of exogenous TGFB1, 2, and 3 inhibited the invasive capacity of these cells in a dose-dependent manner. Proliferation of trophoblast in the placental explants did not alter in response to any of the cytokines tested. Apoptosis of villous and extravillous trophoblast did not alter in response to TGFB1, 2, and 3. There was a reduction in secreted levels of matrix metalloproteinase (MMP) 9 and urokinase plasminogen activator in response to all three cytokines. MMP2 and tissue inhibitor of metalloproteinase 1 and 3 levels were not altered. These results suggest that TGFB1, 2, and 3 inhibit trophoblast invasion by a mechanism dependent on reduced protease activity. © 2005 by the Society for the Study of Reproduction, Inc.


Publication metadata

Author(s): Lash GE, Otun HA, Innes BA, Bulmer JN, Searle RF, Robson SC

Publication type: Article

Publication status: Published

Journal: Biology of Reproduction

Year: 2005

Volume: 73

Issue: 2

Pages: 374-381

ISSN (print): 0006-3363

ISSN (electronic): 1529-7268

Publisher: Society for the Study of Reproduction

URL: http://dx.doi.org/10.1095/biolreprod.105.040337

DOI: 10.1095/biolreprod.105.040337

PubMed id: 15858216


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