Fetuin-A (alpha 2HS glycoprotein) modulates growth, motility, invasion, and senescence in high-grade astrocytomas

作者：Nangami Gladys N; Sakwe Amos M; Izban Michael G; Rana Tanu; Lammers Philip E; Thomas Portia; Chen Zhenbang; Ochieng Josiah^*

来源：Cancer Medicine, 2016, 5(12): 3532-3543.

DOI：10.1002/cam4.940

• Fetuin-A
• glioblastoma
• growth
• invasion
• motility
• senescence

Glioblastomas (high-grade astrocytomas) are highly aggressive brain tumors with poor prognosis and limited treatment options. In the present studies, we have defined the role of fetuin-A, a liver-derived multifunctional serum protein, in the growth of an established glioblastoma cell line, LN229. We hereby demonstrate that these cells synthesize ectopic fetuin-A which supports their growth in culture in the absence of serum. We have demonstrated that a panel of tissue microarray (TMA) of glioblastomas also express ectopic fetuin-A. Knocking down fetuin-A using shRNA approach in LN229, significantly reduced their in vitro growth as well as growth and invasion in vivo. The fetuin-A knockdown subclones of LN229 (A and D) also had reduced motility and invasive capacity. Treatment of LN229 cells with asialofetuin (ASF), attenuated their uptake of labeled fetuin-A, and induced senescence in them. Interestingly, the D subclone that had similar to 90% reduction in ectopic fetuin-A, underwent senescence in serum-free medium which was blunted in the presence of purified fetuin-A. Uptake of labeled exosomes was attenuated in fetuin-A knockdown subclones A and D. Taken together, the studies demonstrate the impact of fetuin-A as significant node of growth, motility, and invasion signaling in glioblastomas that can be targeted for therapy.

• 出版日期2016-12