Department of Diagnostic Pathology, School of Medicine, Fukushima Medical University, Fukushima, Japan.
Int J Oncol. 2015 Mar;46(3):973-80. doi: 10.3892/ijo.2015.2818. Epub 2015 Jan 7.
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.
细胞表面糖链与细胞外基质（ECM）之间的相互作用，包括半乳糖凝集素的相互作用，与肿瘤细胞的黏附、侵袭和转移密切相关。我们分析了细胞表面唾液酸化或糖基化在半乳糖凝集素或 ECM 介导的人恶性淋巴瘤细胞黏附和侵袭中的作用。节杆菌属尿酸酶（AU）处理导致我们实验室建立的人间变性大细胞淋巴瘤（H-ALCL）细胞对半乳糖凝集素-8的黏附减少。siRNA 敲低 β-半乳糖苷 α-2,6-唾液酸转移酶（ST6Gal1）导致 H-ALCL 细胞细胞质中 ST6Gal1 表达抑制，并显著增强对半乳糖凝集素-8的黏附。另一方面，α-2,3-特异性神经氨酸酶处理导致对半乳糖凝集素-8的黏附适度增强。我们通过用苄基 2-乙酰氨基-2-脱氧-α-D-半乳糖吡喃糖苷（Bz-α-GalNAc）处理 H-ALCL 来进行细胞表面 O-聚糖的化学人工修饰。用 Bz-α-GalNAc 处理可增强细胞对半乳糖凝集素-8 的黏附，表明抑制 O-聚糖的延伸可能增强 H-ALCL 细胞对半乳糖凝集素-8 的黏附。另一方面，用衣霉素（TM）抑制 N-糖基化的延伸导致 Phaseolus vulgaris-L（L-PHA）凝集素结合活性抑制，并抑制细胞对半乳糖凝集素-8、层粘连蛋白和纤维连接蛋白的黏附。神经氨酸酶处理增强了细胞对层粘连蛋白的黏附，ST6Gal1 的敲低导致细胞对层粘连蛋白的黏附增强，但对纤维连接蛋白、胶原蛋白 1 和 4 没有影响。半乳糖凝集素-8 预处理显著增强了细胞对层粘连蛋白的黏附，神经氨酸酶处理也增强了半乳糖凝集素-8 与层粘连蛋白的组合对细胞的黏附。Rho 抑制剂 C3-转移酶预处理抑制了细胞对半乳糖凝集素-8 的侵袭。磷脂酰肌醇 3-磷酸激酶（PI3K）抑制剂渥曼青霉素抑制了细胞对半乳糖凝集素-8 的侵袭能力。神经氨酸酶处理通过半乳糖凝集素-8 诱导淋巴瘤细胞生长抑制。
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