Human chorionic gonadotropin beta (HCGbeta) down-regulates E-cadherin and promotes human prostate carcinoma cell migration and invasion.
BACKGROUND
Membrane-associated human chorionic gonadotropin beta (HCGbeta) is correlated with a poor prognosis in localized prostate adenocarcinoma. The relationship between HCGbeta and metastasis, however, is unclear.


METHODS
To shed some light on the issue, two stable prostate carcinoma cell lines overexpressing HCGbeta, designated DU145 HCGbeta and PC3 HCGbeta, were created and compared with empty vector stably transfected DU145 and PC3 cells (control cells).


RESULTS
HCGbeta expression resulted in a change in morphology; the cells were more elongated and had multiple pseudopodia, while the control cells were more rounded. This change in morphology was duplicated by incubating control cells in conditioned medium from the DU145 HCGbeta or PC3 HCGbeta cells, or by adding purified HCGbeta to control medium. The DU145 HCGbeta and PC3 HCGbeta cells were also less adherent than the controls, as assessed by the ease with which trypsin-EDTA could remove them from culture plates. Reduced adherence could be duplicated by incubation of control cells with either conditioned medium or purified HCGbeta. Western blot analysis showed that DU145 HCGbeta and PC3 HCGbeta cells expressed less E-cadherin than control cells and that a change of medium increased expression of E-cadherin. Addition of conditioned medium, or purified HCGbeta, to control cells down-regulated E-cadherin. Cell migration and invasion assays showed that DU145 HCGbeta and PC3 HCGbeta cells were more migratory and invasive than controls and that treatment of control cells with either conditioned medium or purified HCGbeta increased their migratory/invasive capacity.


CONCLUSIONS
The data indicate that HCGbeta is directly responsible for changes in prostate carcinoma cells associated with an increased metastatic phenotype.
Wu
Wei
W
Division of Biomedical Sciences, University of California, Riverside, California 92521-0121, USA.
Walker
Ameae M
AM
D015820:Cadherins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D002465:Cell Movement; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000378:metabolism* / Q000494:pharmacology; D003001:Cloning, Molecular; D003094:Collagen / Q000737:chemistry; D017077:Culture Media, Conditioned; D015536:Down-Regulation; D004338:Drug Combinations; D006801:Humans; D007797:Laminin / Q000737:chemistry; D008297:Male; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011509:Proteoglycans / Q000737:chemistry
D015820:Cadherins; D018997:Chorionic Gonadotropin, beta Subunit, Human; D017077:Culture Media, Conditioned; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen