The role of protein glycosylation inhibitors in the prevention of metastasis and therapy of cancer
The role of protein glycosylation inhibitors in the prevention of metastasis and therapy of cancer
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DOI：
10.1046/j.1525-1500.1998.00054.x
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发表时间：
1998-01-01
影响因子：
--
通讯作者：
Olden, K
中科院分区：
文献类型：
--
作者：
Roberts, JD;Klein, JLD;Olden, K
细胞表面糖蛋白的寡糖部分被认为参与癌症转移和侵袭过程中的识别事件。苦马豆素是高尔基体 α-甘露糖苷酶 II 的抑制剂，已被证明可以阻止肿瘤细胞在肺部定植并刺激免疫系统的组成部分。苦马豆素还可以消除化疗药物的大部分毒性并刺激骨髓造血祖细胞，这表明其具有其他治疗用途。我们目前正在表征苦马豆素改变人和小鼠骨髓祖细胞生长的能力。此外，我们正在研究转移中依赖于在细胞-基质相互作用中发挥作用的细胞表面分子的关键步骤。我们的工作表明，顺式多不饱和脂肪酸会快速刺激肿瘤细胞在体外对 IV 型胶原蛋白的粘附，并且依赖于蛋白激酶 C 活性。我们正在研究整合素是这种粘附的关键组成部分的假设，并正在研究导致细胞粘附调节的潜在信号转导途径。
Oligosaccharide moieties of cell-surface glycoproteins are thought to be involved in recognition events during cancer metastasis and invasion. Swainsonine, an inhibitor of the Golgi alpha-mannosidase II, has been shown to block pulmonary colonization by tumor cells and stimulate components of the immune system. Swainsonine also abrogates much of the toxicity of chemotherapeutic agents and stimulates bone marrow hematopoietic progenitor cells, suggesting additional therapeutic applications. We are currently characterizing the ability of swainsonine to modify cell growth in human and murine bone marrow progenitor cells. Furthermore, we are examining crucial steps in metastasis that depend upon cell surface molecules that play a role in cell-matrix interactions. Our work shows that tumor cell adhesion to collagen IV in vitro is rapidly stimulated by cis-polyunsaturated fatty acids and is dependent on protein kinase C activity. We are investigating the hypothesis that integrins are critical components of this adhesion and are examining potential signal transduction pathways that lead to the modulation of cell adhesion.