Abstract: 253

MECHANISM OF INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN (IGFBP)-1 MEDIATED STIMULATION OF EXTRAVILLOUS TROPHOBLAST MIGRATION.

Louise Gleeson¹ , Chandan Chakraborty¹ , Timothy McKinnon¹ , Peeyush Lala^{1 *}
Dept.of Anatomy & Cell Biology, University of Western Ontario, London ONT, Canada ¹

It has been shown that insulin-like growth factor (IGF)-II mRNA is expressed by human invasive extravillous trophoblast (EVT) in situ, while insulin-like growth factor binding protein (IGFBP)-1 mRNA is expressed by the decidual cells in close proximity, indicating that these molecules serve as signals for EVT-decidual interaction. Indeed our laboratory has shown that both molecules can independently stimulate EVT cell migration (Irving and Lala, 1995) and invasion (Hamilton et al, 1998). In the present study we utilized EVT cells in culture and an in vitro TranswellŽ migration assay to test whether migration stimulating effects of IGFBP-1 depend on binding of the RGD domain of this molecule to a51 integrin selectively expressed by EVT cells, followed by intracellular signaling via MAPK pathway. Results revealed that: 1) treatment with recombinant IGFBP-1 (0.5 nM) caused a significant increase in migration of EVT cells, whereas a polyclonal antibody (Ab) against a51 integrin blocked migration in the presence or absence of IGFBP-1, 2) addition of a GRGDSP, but not a GRGESP, pentapeptide abrogated the migration stimulation by IGFBP-1, 3) when IGFBP-1 was mutated at the RGD domain to WGD (Clemmons DR), the migration stimulating function was lost, 4) pre-incubation of EVT cells with a MEK inhibitor PD 098059 caused a significant decrease in migration in the presence or absence of IGFBP-1. These results suggest that IGFBP-1 directly stimulates EVT cell migration by binding to the a51 integrin on the EVT cell surface via its RGD domain; and that this binding leads to signal transduction via MAPK pathway. (Supported by MRC Canada)

    This abstract is being presented on Monday, August 2 at 8:00 AM to 10:15 AM at CUB 2nd Floor Ballroom.