title: Annexin A2 promotes glioma cell invasion and tumor progression.
abstract: Gliomas are highly invasive, lethal brain tumors. Tumor-associated proteases play an important role in glioma progression. Annexin A2 is overexpressed in many cancers and correlates with increased plasmin activity on the tumor cell surface, which mediates degradation of extracellular matrix and promotes neoangiogenesis to facilitate tumor growth. In this study, we used two glioma cell lines, mouse GL261-EGFP and rat C6/LacZ, as well as stable clones transfected with an annexin A2 knockdown construct. We find that the annexin A2 knockdown decreased glioma cell migration in vitro and decreased membrane-bound plasmin activity. In vivo, we injected the glioma cells into the rodent brain and followed glioma progression. Knockdown of annexin A2 in glioma cells decreased tumor size and slowed tumor progression, as evidenced by decreased invasion, angiogenesis, and proliferation, as well as increased apoptosis in the tumor tissue of the annexin A2 knockdown group. Moreover, we report that the levels of expression of annexin A2 in human glioma samples correlate with their degree of malignancy. Together, our findings demonstrate that inhibition of annexin A2 expression in glioma cells could become a new target for glioma therapy.
authors: Molecular and Cellular Biology Program, Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York 11794, USA.
authors: Haiyan
authors: H
authors: Zhai
authors: Suchitra
authors: S
authors: Acharya
authors: Iordanis
authors: I
authors: Gravanis
authors: Saira
authors: S
authors: Mehmood
authors: Roberta J
authors: RJ
authors: Seidman
authors: Kenneth R
authors: KR
authors: Shroyer
authors: Katherine A
authors: KA
authors: Hajjar
authors: Stella E
authors: SE
authors: Tsirka
mesh_terms: D000818:Animals; D017306:Annexin A2 / Q000096:biosynthesis*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002460:Cell Line; D045744:Cell Line, Tumor; D018450:Disease Progression; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009361:Neoplasm Invasiveness / Q000473:pathology; D010865:Pilot Projects; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D017306:Annexin A2