The role of  5 1-integrin in the IGF-I-induced migration of extravillous trophoblast cells during the process of implantation

• Published in: Molecular human reproduction 2004-02, Vol.10 (2), p.91-97
• Main Authors: Kabir-Salmani, M, Shiokawa, S, Akimoto, Y, Sakai, K, Iwashita, M
• Format: Article
• Language: English
• ISSN: 1460-2407; 1360-9947; 1460-2407
• DOI: 10.1093/molehr/gah014

The role of integrins in the processes of adhesion and migration makes them attractive potential participants in the complex events of embryo implantation and placentation. Recently, the role of the [alpha]v[beta]3-integrin pathway was shown in the insulin-like growth factor-I (IGF-I)-stimulated migration of extravillous trophoblast (EVT) cells. This study was designed to investigate the role of [alpha]5[beta]1-integrin in this respect. Using cultured EVT cells, migration assays were carried out for IGF-I-treated or untreated cells in the presence or absence of the GRGDSP and GRGESP hexapeptides, [alpha]IR3, and a blocking antibody against [alpha]5[beta]1-integrin. Immuno-electron microscopy and immunofluorescent staining were performed to localize the distribution of [alpha]5[beta]1- and [alpha]v[beta]3-integrins, Rab5a, paxillin, phospho-FAK (pFAK), and vinculin. The results showed that IGF-I-induced migration of EVT cells was abolished following treatment with GRGDSP hexapeptide, [alpha]IR3, and a blocking antibody against [alpha]5[beta]1-integrin. Further, statistical analysis showed that the area-related numerical density of the [alpha]5[beta]1-integrin in the perinuclear regions was significantly higher than in the cell extensions. Immunocytochemical experiments demonstrated an up-regulation in internalization rate of [alpha]5[beta]1-integrin in IGF-I-stimulated EVT cells. Furthermore, [alpha]5[beta]1-integrin exhibited co-localization with Rab5a, but not with [alpha]v[beta]3-integrin, pFAK, paxillin, and vinculin at the focal adhesions of the EVT cells. Taken together, these findings suggest an essential role for [alpha]5[beta]1-integrin in IGF-I-promoted migration of EVT cells. It is possible therefore that IGF-I-induced internalization of [alpha]5[beta]1-integrin may be an important event during the migration of EVT cells in the complex processes of implantation and placentation.