Growth as a solid tumor or reduced glucose concentrations in culture reversibly induce CD44-mediated hyaluronan recognition by Chinese hamster ovary cells.
Growth as a solid tumor or reduced glucose concentrations in culture reversibly induce CD44-mediated hyaluronan recognition by Chinese hamster ovary cells.
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DOI：
10.1172/jci119635
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发表时间：
1997-09
期刊：
影响因子：
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通讯作者：
Zhong Zheng;Richard D. Cummings;Philip E. Pummill;Paul W. Kincade
中科院分区：
文献类型：
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作者：
Zhong Zheng;Richard D. Cummings;Philip E. Pummill;Paul W. Kincade
CD44的密度、分子亚型和翻译后修饰可以显著影响肿瘤的生长和转移行为。CD44的许多功能，包括一些与肿瘤有关的功能，都被归因于它识别透明质酸(HA)的能力。然而，只有某些携带CD44的细胞才能结合可溶性或固定化的HA。我们现在发现，由野生型中国仓鼠卵巢细胞(CHO-K1)和一个配体结合亚克隆产生的CD44在N-连接糖基化方面存在差异。两者都携带高度分枝的复合型糖形式的CD44，而野生型表达的CD44更广泛地被唾液酸化。CHO-K1细胞在培养时无法识别HA，当作为实体瘤生长时获得了这种能力，并在返回培养时恢复到非HA结合状态。当培养液中葡萄糖浓度降低时，CHO-K1细胞识别HA的能力也被可逆地诱导。葡萄糖限制通过许多但不是全部影响CD44介导的HA与一系列小鼠肿瘤的结合。葡萄糖浓度和糖基化抑制剂仅部分影响静息小鼠B淋巴细胞上CD44受体的功能。这些观察表明，葡萄糖水平或其他局部环境条件可能显著影响某些肿瘤细胞使用的糖基化途径，导致CD44介导的功能发生显著变化。
The density, molecular isoform, and posttranslational modifications of CD44 can markedly influence growth and metastatic behavior of tumors. Many CD44 functions, including some involving tumors, have been attributed to its ability to recognize hyaluronan (HA). However, only certain CD44-bearing cells bind soluble or immobilized HA. We now show that CD44 made by wild-type Chinese hamster ovary (CHO-K1) cells and a ligand-binding subclone differ with respect to N-linked glycosylation. While both bear CD44 with highly branched, complex-type glycoforms, CD44 expressed by the wild type was more extensively sialylated. CHO-K1 cells which failed to recognize HA when grown in culture gained this ability when grown as a solid tumor and reverted to a non-HA-binding state when returned to culture. The ability of CHO-K1 cells to recognize HA was also reversibly induced when glucose concentrations in the medium were reduced. Glucose restriction influenced CD44-mediated HA binding by many but not all, of a series of murine tumors. Glucose concentrations and glycosylation inhibitors only partially influenced CD44 receptor function on resting murine B lymphocytes. These observations suggest that glucose levels or other local environmental conditions may markedly influence glycosylation pathways used by some tumor cells, resulting in dramatic alteration of CD44-mediated functions.