title: Fetuin-A (alpha 2HS glycoprotein) modulates growth, motility, invasion, and senescence in high-grade astrocytomas.
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.
authors.affiliation: Department of Biochemistry and Cancer Biology, Meharry Medical College, 1005 D.B. Todd Blvd., Nashville, 37208, Tennessee.
authors.forename: Gladys N
authors.initials: GN
authors.lastname: Nangami
authors.affiliation: Department of Biochemistry and Cancer Biology, Meharry Medical College, 1005 D.B. Todd Blvd., Nashville, 37208, Tennessee.
authors.forename: Amos M
authors.initials: AM
authors.lastname: Sakwe
authors.affiliation: Departments of Pathology, Meharry Medical College, 1005 D.B. Todd Blvd., Nashville, 37208, Tennessee.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Izban
authors.affiliation: Department of Biochemistry and Cancer Biology, Meharry Medical College, 1005 D.B. Todd Blvd., Nashville, 37208, Tennessee.
authors.forename: Tanu
authors.initials: T
authors.lastname: Rana
authors.affiliation: Department of Internal Medicine, Meharry Medical College, 1005 D.B. Todd Blvd., Nashville, 37208, Tennessee.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Lammers
authors.affiliation: Department of Biochemistry and Cancer Biology, Meharry Medical College, 1005 D.B. Todd Blvd., Nashville, 37208, Tennessee.
authors.forename: Portia
authors.initials: P
authors.lastname: Thomas
authors.affiliation: Department of Biochemistry and Cancer Biology, Meharry Medical College, 1005 D.B. Todd Blvd., Nashville, 37208, Tennessee.
authors.forename: Zhenbang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Cancer Biology, Meharry Medical College, 1005 D.B. Todd Blvd., Nashville, 37208, Tennessee.
authors.forename: Josiah
authors.initials: J
authors.lastname: Ochieng
mesh_terms: D000818:Animals; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics; D004195:Disease Models, Animal; D055354:Exosomes / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D060787:Neoplasm Grading; D060749:alpha-2-HS-Glycoprotein / Q000235:genetics* / Q000378:metabolism
chemical_list: D060749:alpha-2-HS-Glycoprotein
keywords: Fetuin-A; glioblastoma; growth; invasion; motility; senescence