The role of α5β1‐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
• Subjects: Biological and medical sciences; Embryology: invertebrates and vertebrates. Teratology; Fundamental and applied biological sciences. Psychology; Key words: α5β1‐integrin/IGF‐I/implantation/placentation/trophoblast migration
• ISSN: 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 αvβ3‐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 α5β1‐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, αIR3, and a blocking antibody against α5β1‐integrin. Immuno‐electron microscopy and immunofluorescent staining were performed to localize the distribution of α5β1‐ and αvβ3‐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, αIR3, and a blocking antibody against α5β1‐integrin. Further, statistical analysis showed that the area‐related numerical density of the α5β1‐integrin in the perinuclear regions was significantly higher than in the cell extensions. Immunocytochemical experiments demonstrated an up‐regulation in internalization rate of α5β1‐integrin in IGF‐I‐stimulated EVT cells. Furthermore, α5β1‐integrin exhibited co‐localization with Rab5a, but not with αvβ3‐integrin, pFAK, paxillin, and vinculin at the focal adhesions of the EVT cells. Taken together, these findings suggest an essential role for α5β1‐integrin in IGF‐I‐promoted migration of EVT cells. It is possible therefore that IGF‐I‐induced internalization of α5β1‐integrin may be an important event during the migration of EVT cells in the complex processes of implantation and placentation.