Open AccessFetuin‐A (alpha 2 HS glycoprotein) modulates growth, motility, invasion, and senescence in high‐grade astrocytomas
Author(s) -
Nangami Gladys N.,
Sakwe Amos M.,
Izban Michael G.,
Rana Tanu,
Lammers Philip E.,
Thomas Portia,
Chen Zhenbang,
Ochieng Josiah
Publication year - 2016
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.940
Subject(s) - fetuin , gene knockdown , biology , cell growth , cancer research , cell culture , motility , in vivo , small hairpin rna , microbiology and biotechnology , ectopic expression , glycoprotein , biochemistry , genetics
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, LN 229. 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 sh RNA approach in LN 229, significantly reduced their in vitro growth as well as growth and invasion in vivo. The fetuin‐A knockdown subclones of LN 229 (A and D) also had reduced motility and invasive capacity. Treatment of LN 229 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.