title: Sialylation by β-galactoside α-2,6-sialyltransferase and N-glycans regulate cell adhesion and invasion in human anaplastic large cell lymphoma.
abstract: The interaction between cell surface glycans and extracellular matrix (ECM) including galectins is known to be closely associated with tumor cell adhesion, invasion and metastasis. We analyzed the roles of cell surface sialylation or glycosylation in galectin or ECM‑mediated cell adhesion and invasion of human malignant lymphoma cells. Neuraminidase from Arthrobacter ureafaciens (AU) treatment resulted in reduction of cell adhesion to galectin‑8 in human anaplastic large cell lymphoma (H‑ALCL) which was established in our laboratory. The knockdown of β‑galactoside α‑2,6‑sialyltrans-ferase (ST6Gal1) by siRNA showed inhibition of ST6Gal1 expression in the cytoplasm of H‑ALCL cells on immunohistochemical findings, and showed dramatic enhancement of cell adhesion to galectin‑8. On the other hand, α‑2,3‑specific neuraminidase treatment resulted in moderate enhancement of cell adhesion to galectin‑8. We performed chemically artificial modification of cell surface O‑glycans by treatment of benzyl 2‑acetamido‑2‑deoxy‑α‑D‑galactopyranoside (Bz‑α‑GalNAc) in H‑ALCL. Cell adhesion to galectin‑8 was enhanced by treatment of Bz‑α‑GalNAc suggesting that inhibition of elongation of O‑glycans may enhance cell adhesion to galectin‑8 in H‑ALCL cells. On the other hand inhibition of elongation of N‑glycosylation by tunicamycin (TM) resulted in inhibition of Phaseolus vulgaris‑L (L‑PHA) lectin‑binding activity and inhibited cell adhesion to galectin‑8, laminin and fibronectin. Neuraminidase treatment enhanced cell adhesion to laminin, and knockdown of ST6Gal1 resulted in enhancement of cell adhesion to laminin, but not to fibronectin, collagen type 1 and 4. Galectin‑8 pre‑treatment dramatically enhanced cell adhesion to laminin and neuraminidase treatment also enhanced cell adhesion to laminin in combination with galectin‑8. Rho inhibitor, C3‑transferase pre‑treatment resulted in inhibition of cell invasion to galectin‑8. Phosphatidylinositol 3‑phosphate kinase (PI3K) inhibitor, wortmannin inhibits the cell invasive capacity to galectin‑8. Neuraminidase treatment induces growth inhibition of lymphoma cells by galectin‑8.
authors.affiliation: Department of Diagnostic Pathology, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Suzuki
authors.affiliation: Department of Diagnostic Pathology, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Abe
authors.affiliation: Department of Diagnostic Pathology, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hashimoto
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor / Q000187:drug effects; D003593:Cytoplasm / Q000201:enzymology; D005353:Fibronectins / Q000378:metabolism; D005690:Galactose / Q000031:analogs & derivatives / Q000494:pharmacology; D037161:Galectins / Q000378:metabolism; D055785:Gene Knockdown Techniques; D005936:Glucans / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D017728:Lymphoma, Large-Cell, Anaplastic / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D009439:Neuraminidase / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D034741:RNA, Small Interfering; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology; D000077191:Wortmannin; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D000730:Androstadienes; D015703:Antigens, CD; D005353:Fibronectins; D005690:Galactose; D037161:Galectins; D005936:Glucans; D007797:Laminin; D009439:Neuraminidase; D010835:Phytohemagglutinins; D034741:RNA, Small Interfering; D012799:Sialyltransferases; D014415:Tunicamycin; D000077191:Wortmannin; C411946:1-benzyl-2-acetamido-2-galactopyranoside; C091991:LGALS8 protein, human; C093493:ST6GAL1 protein, human; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase