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 ECMmediated cell adhesion and invasion of human malignant lymphoma cells. Neuraminidase from Arthrobacter ureafaciens (AU) treatment resulted in reduction of cell adhesion to galectin8 in human anaplastic large cell lymphoma (HALCL) which was established in our laboratory. The knockdown of betagalactoside alpha2,6sialyltrans-ferase (ST6Gal1) by siRNA showed inhibition of ST6Gal1 expression in the cytoplasm of HALCL cells on immunohistochemical findings, and showed dramatic enhancement of cell adhesion to galectin8. On the other hand, alpha2,3specific neuraminidase treatment resulted in moderate enhancement of cell adhesion to galectin8. We performed chemically artificial modification of cell surface Oglycans by treatment of benzyl 2acetamido2deoxyalphaDgalactopyranoside (BzalphaGalNAc) in HALCL. Cell adhesion to galectin8 was enhanced by treatment of BzalphaGalNAc suggesting that inhibition of elongation of Oglycans may enhance cell adhesion to galectin8 in HALCL cells. On the other hand inhibition of elongation of Nglycosylation by tunicamycin (TM) resulted in inhibition of Phaseolus vulgarisL (LPHA) lectinbinding activity and inhibited cell adhesion to galectin8, 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. Galectin8 pretreatment dramatically enhanced cell adhesion to laminin and neuraminidase treatment also enhanced cell adhesion to laminin in combination with galectin8. Rho inhibitor, C3transferase pretreatment resulted in inhibition of cell invasion to galectin8. Phosphatidylinositol 3phosphate kinase (PI3K) inhibitor, wortmannin inhibits the cell invasive capacity to galectin8. Neuraminidase treatment induces growth inhibition of lymphoma cells by galectin8.