title: Human chorionic gonadotropin and its free β-subunit stimulate trophoblast invasion independent of LH/hCG receptor.
abstract: Both paracrine and autocrine factors are involved in the regulation of trophoblast invasion. One of these factors is human chorionic gonadotropin (hCG), which stimulates trophoblast invasion. The stimulatory activity has especially been ascribed to a hyperglycosylated form of hCG (hCG-h) that is expressed in early pregnancy. We compared the stimulatory activities of different forms of hCG and its free β-subunit (hCGβ) on trophoblast invasion. hCG, hCG-h, hCGβ, and its hyperglycosylated form (hCGβ-h) stimulated the invasion of JEG-3 choriocarcinoma cells. The stimulatory effect of hCGβ was also confirmed with primary human trophoblasts. Down-regulation of the LH/hCG receptor by RNA-interference did not significantly reduce the effect of hCGβ and hCG on cell invasion. Increased invasion was associated with increased levels of MMP-2, MMP-9 and activity of uPA. Our findings suggest that hCG, hCGβ and their hyperglycosylated forms stimulate the invasion of trophoblast cells independent of the classical LH/hCG-receptor.
authors.affiliation: Department of Obstetrics and Gynecology, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, Hong Kong Special Administrative Region. kcllee@hku.hk
authors.forename: Cheuk-Lun
authors.initials: CL
authors.lastname: Lee
authors.forename: Philip C N
authors.initials: PC
authors.lastname: Chiu
authors.forename: Laura
authors.initials: L
authors.lastname: Hautala
authors.forename: Tuula
authors.initials: T
authors.lastname: Salo
authors.forename: William S B
authors.initials: WS
authors.lastname: Yeung
authors.forename: Ulf-Håkan
authors.initials: UH
authors.lastname: Stenman
authors.forename: Hannu
authors.initials: H
authors.lastname: Koistinen
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D006063:Chorionic Gonadotropin / Q000502:physiology; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000502:physiology*; D010064:Embryo Implantation; D004790:Enzyme Induction; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D014327:Trophoblasts / Q000502:physiology*; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D034741:RNA, Small Interfering; D011974:Receptors, LH; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D014568:Urokinase-Type Plasminogen Activator; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9