Integrin alpha5 is involved in fibronectin-induced human extravillous trophoblast invasion.
To identify the molecules involved in human extravillous trophoblast (EVT) invasion, we raised murine mAbs that react with EVTs and obtained one mAb (CHL3) that inhibited invasion of a human choriocarcinoma-derived cell line, BeWo cells. The N-terminal 22 aminoacid sequence of the CHL3 antigen (150kDa) purified from placental tissue completely matched that of integrin alpha5, which is known to interact with fibronectin. Double immunohistochemical staining and flow cytometry confirmed the reactivity of CHL3 with integrin alpha5 and its expression on the surface of BeWo cells and human EVTs isolated from villous explant cultures. CHL3 mAb inhibited the attachment of human EVTs and BeWo cells to fibronectin-coated dishes, but not to Matrigel dishes. In the Matrigel invasion assay supplemented with or without fibronectin, the invasion of isolated EVTs and BeWo cells was attenuated by treatment with CHL3 without affecting cell proliferation. During invasion assays, the production of matrix metalloproteases 2 and 9 was not changed by CHL3. These findings suggest that interaction with fibronectin through integrin alpha5 plays an important role in human extravillous trophoblast invasion.
Zeng
Bin-Xiang
BX
Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Fujiwara
Hiroshi
H
Sato
Yukiyasu
Y
Nishioka
Yoshihiro
Y
Yamada
Shigetoshi
S
Yoshioka
Shinya
S
Ueda
Masamichi
M
Higuchi
Toshihiro
T
Fujii
Shingo
S
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001681:Biological Assay; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005353:Fibronectins / Q000378:metabolism* / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D039482:Integrin alpha5 / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D010920:Placenta / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D010929:Placentation; D011247:Pregnancy; D014327:Trophoblasts / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D039482:Integrin alpha5