Human chorionic gonadotropin β (HCGβ) down‐regulates E‐cadherin and promotes human prostate carcinoma cell migration and invasion

BACKGROUND Membrane‐associated human chorionic gonadotropin β (HCGβ) is correlated with a poor prognosis in localized prostate adenocarcinoma. The relationship between HCGβ and metastasis, however, is unclear. METHODS To shed some light on the issue, two stable prostate carcinoma cell lines overexpressing HCGβ, designated DU145 HCGβ and PC3 HCGβ, were created and compared with empty vector stably transfected DU145 and PC3 cells (control cells). RESULTS HCGβ 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 HCGβ or PC3 HCGβ cells, or by adding purified HCGβ to control medium. The DU145 HCGβ and PC3 HCGβ 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 HCGβ. Western blot analysis showed that DU145 HCGβ and PC3 HCGβ 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 HCGβ, to control cells down‐regulated E‐cadherin. Cell migration and invasion assays showed that DU145 HCGβ and PC3 HCGβ cells were more migratory and invasive than controls and that treatment of control cells with either conditioned medium or purified HCGβ increased their migratory/invasive capacity. CONCLUSION The data indicate that HCGβ is directly responsible for changes in prostate carcinoma cells associated with an increased metastatic phenotype. Cancer 2006. © 2005 American Cancer Society.