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Integrin-Linked Kinase (ILK) Is Highly Expressed in First Trimester Human Chorionic Villi and Regulates Migration of a Human Cytotrophoblast-Derived Cell Line¹

Division of Basic Medical Sciences,³ Health Sciences Centre, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada A1B 3V6 Department of Laboratory Medicine and Pathobiology,⁴ University of Toronto and Cancer Research Program, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X5 Program in Development and Fetal Health,⁵ Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ontario, Canada M5G 1X5

ABSTRACT

The placenta represents a critically important fetal-maternal interaction. Trophoblast migration and invasion into the uterine wall is a precisely controlled process and aberrations in these processes are implicated in diseases such as preeclampsia. Integrin-linked kinase (ILK) is a multifunctional, cytoplasmic, serine/threonine kinase that has been implicated in regulating processes such as cell proliferation, survival, migration, and invasion; yet the temporal and spatial pattern of expression of ILK in human chorionic villi and its role in early human placental development are completely unknown. We hypothesized that ILK would be expressed in trophoblast subtypes of human chorionic villi during early placental development and that it would regulate trophoblast migration. Immunoblot analysis revealed that ILK protein was highly detectable in placental tissue samples throughout gestation. In floating branches of chorionic villi, from 6 to 15 wk of gestation immunofluorescence analysis of ILK expression in placental tissue sections demonstrated that ILK was highly detectable in the cytoplasm and membranes of villous cytotrophoblast cells and in stromal mesenchyme, whereas it was barely detectable in the syncytiotrophoblast layer. In anchoring branches of villi, ILK was highly localized to plasma membranes of extravillous trophoblast cells. Transient expression of dominant negative E359K-ILK in the villous explant-derived trophoblast cell line HTR8-SVneo dramatically reduced migration into wounds compared to cells expressing wild-type ILK or empty vector. Therefore, our work has demonstrated that ILK is highly expressed in trophoblast subtypes of human chorionic villi during the first trimester of pregnancy and is a likely mediator of trophoblast migration during this period of development.

developmental biology, kinases, placenta, pregnancy, trophoblast

¹ Supported by Canadian Institutes of Health Research grant 64731, Industrial Research and Innovation Fund grant 0405-014 (Province of Newfoundland and Labrador), and Canada Foundation for Innovation New Opportunities Fund 74119.

² Correspondence: Daniel MacPhee, Division of Basic Medical Sciences, Health Sciences Centre, Rm. 5340B, 300 Prince Philip Dr., St. John's, Newfoundland and Labrador A1B 3V6, Canada. FAX: 709 777 7010; dmacphee{at}mun.ca