Human chorionic gonadotropin and its free β-subunit stimulate trophoblast invasion independent of LH/hCG receptor

Cheuk-Lun Lee; Philip C N Chiu; Laura Hautala; Tuula Salo; William S B Yeung; Ulf-Håkan Stenman; Hannu Koistinen

doi:10.1016/j.mce.2013.05.009

Human chorionic gonadotropin and its free β-subunit stimulate trophoblast invasion independent of LH/hCG receptor

Mol Cell Endocrinol. 2013 Aug 15;375(1-2):43-52. doi: 10.1016/j.mce.2013.05.009. Epub 2013 May 17.

Authors

Cheuk-Lun Lee¹, Philip C N Chiu, Laura Hautala, Tuula Salo, William S B Yeung, Ulf-Håkan Stenman, Hannu Koistinen

Affiliation

¹ 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

PMID: 23684886
DOI: 10.1016/j.mce.2013.05.009

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cell Movement
Cell Proliferation
Chorionic Gonadotropin / physiology
Chorionic Gonadotropin, beta Subunit, Human / physiology*
Embryo Implantation*
Enzyme Induction
Female
Gene Expression
Gene Knockdown Techniques
Humans
Male
Matrix Metalloproteinase 2 / genetics
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 9 / genetics
Matrix Metalloproteinase 9 / metabolism
Protein Binding
RNA, Small Interfering / genetics
Receptors, LH / genetics
Receptors, LH / metabolism*
Tissue Inhibitor of Metalloproteinase-1 / genetics
Tissue Inhibitor of Metalloproteinase-1 / metabolism
Tissue Inhibitor of Metalloproteinase-2 / genetics
Tissue Inhibitor of Metalloproteinase-2 / metabolism
Trophoblasts / physiology*
Urokinase-Type Plasminogen Activator / genetics
Urokinase-Type Plasminogen Activator / metabolism

Substances

Chorionic Gonadotropin
Chorionic Gonadotropin, beta Subunit, Human
RNA, Small Interfering
Receptors, LH
TIMP1 protein, human
TIMP2 protein, human
Tissue Inhibitor of Metalloproteinase-1
Tissue Inhibitor of Metalloproteinase-2
Urokinase-Type Plasminogen Activator
MMP2 protein, human
Matrix Metalloproteinase 2
MMP9 protein, human
Matrix Metalloproteinase 9