Fetuin‐A (alpha 2HS glycoprotein) modulates growth, motility, invasion, and senescence in high‐grade astrocytomas. (23rd November 2016)

• Record Type: Journal Article
• Authors: Nangami, Gladys N.; Sakwe, Amos M.; Izban, Michael G.; Rana, Tanu; Lammers, Philip E.; Thomas, Portia; Chen, Zhenbang; Ochieng, Josiah
• Is Part Of: Cancer medicine. Volume 5:Number 12(2016:Dec.)
• Page Start: 3532
• Page End: 3543
• Publication Date: 2016-11-23
• Subjects: Fetuin‐A -- glioblastoma -- growth -- invasion -- motility -- senescence; 616.994005
• DOI: 10.1002/cam4.940
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: 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 ~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. Abstract : We hereby show that fetuin‐A (ahsg) synthesized by high‐grade astrocytoma cells promote their growth, motility, and invasive capacity. Knockdown of this protein reduces growth, motility, and invasive capacities of these cells in in vitro as well as in vivo assays. Taken together, the data suggest that fetuin‐A is involved in novel epigenetic growth regulation of high‐grade astrocytoma (glioblastoma) cells and can be targeted for therapy of this deadly brain tumor.