Open AccessHuman chorionic gonadotropin β induces cell motility via ERK1/2 and MMP-2 activation in human glioblastoma U87MG cells
Author(s) -
Zongwen Li,
Lianlian Du,
Chunliu Li,
Wei Wu
Publication year - 2012
Publication title -
journal of neuro-oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.256
H-Index - 114
eISSN - 1573-7373
pISSN - 0167-594X
DOI - 10.1007/s11060-012-1017-y
Subject(s) - human chorionic gonadotropin , downregulation and upregulation , cancer research , motility , cell culture , western blot , signal transduction , carcinogenesis , biology , transfection , cell growth , u87 , cell migration , medicine , endocrinology , chemistry , microbiology and biotechnology , cancer , glioblastoma , hormone , biochemistry , genetics , gene
Human chorionic gonadotropin β (hCGβ) promotes tumorigenesis in a variety of tumors including glioblastoma, breast and prostate cancer cells, etc. However, the involved mechanisms remain elusive. Distinct from the other tumors, glioblastoma is a highly invasive brain tumor; invasion causes high recurrence and mortality. Characterization of hCGβ signaling is to determine therapeutic targets to inhibit invasion and lower recurrence. Through both a stable cell line over-expressing hCGβ and hCGβ standards, we tested hCGβ signaling, migration and invasion in human glioblastoma U87MG cells. ELISA showed that hCGβ secreted into culture medium at an amount of 237.8 ± 7.8 ng/10(7) cells in hCGβ transfected stable cells after the cells were grown for 24 h. Through Western blot and Gelatin zymography, we found that hCGβ standards phosphorylated ERK1/2 and upregulated MMP-2 expression in dose- and time-dependent manners. Meanwhile, overexpressed hCGβ phosphorylated ERK1/2, and upregulated MMP-2 expression and activity, whereas ERK1/2 blocker PD98059 (25 μM) significantly decreased both ERK1/2 and MMP-2 expression and activity. In addition, in the same conditions as the signaling test, hCGβ promoted cell migration and invasion, whereas the PD98059 diminished these effects. These findings demonstrated that hCGβ phosphorylated ERK1/2 upregulating MMP-2 expression and activity leading to cell migration and invasion, suggesting that hCGβ, ERK1/2 and MMP-2 are the potential targets to inhibit glioblastoma invasion.