Interaction between CD44 and hyaluronate is directly implicated in the regulation of tumor development.
Interaction between CD44 and hyaluronate is directly implicated in the regulation of tumor development.
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DOI：
10.1084/jem.180.1.53
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发表时间：
1994-07-01
期刊：
影响因子：
--
通讯作者：
Stamenkovic I
中科院分区：
文献类型：
--
作者：
Bartolazzi A;Peach R;Aruffo A;Stamenkovic I
CD 44参与肿瘤生长和转移的调节，但不同CD 44亚型的表达决定原发性和继发性肿瘤生长速率的机制仍不清楚。在本研究中，我们使用野生型和突变形式的CD 44转染的人黑色素瘤，以确定CD 44分子的功能特性是影响肿瘤行为的关键。我们表明，野生型CD 44亚型的表达，结合透明质酸增强了体内黑色素瘤细胞的肿瘤形成的速度，而表达的CD 44突变体，不介导细胞附着到透明质酸，未能做到这一点。可溶性野生型和突变型CD 44-IG融合蛋白对体内黑色素瘤生长的不同抑制作用强调了CD 44-透明质酸相互作用在肿瘤发展中的重要性。然而，局部给予突变的、非透明质酸结合的CD 44-IG融合蛋白对小鼠皮下黑色素瘤生长没有影响，而输注野生型CD 44-IG显示出阻断肿瘤发展。总之，这些观察结果表明，CD 44的肿瘤生长促进特性在很大程度上取决于其介导细胞附着到透明质酸盐的能力。
CD44 is implicated in the regulation of tumor growth and metastasis but the mechanism by which expression of different CD44 isoforms determines the rate of primary and secondary tumor growth remains unclear. In the present study we use a human melanoma transfected with wild-type and mutant forms of CD44 to determine which functional property of the CD44 molecule is critical in influencing tumor behavior. We show that expression of a wild-type CD44 isoform that binds hyaluronic acid augments the rapidity of tumor formation by melanoma cells in vivo, whereas expression of a CD44 mutant, which does not mediate cell attachment to hyaluronate, fails to do so. The importance of CD44- hyaluronate interaction in tumor development is underscored by the differential inhibitory effect of soluble wild-type and mutant CD44-Ig fusion proteins on melanoma growth in vivo. Whereas local administration of a mutant, nonhyaluronate binding, CD44-Ig fusion protein has no effect on subcutaneous melanoma growth in mice, infusion of wild-type CD44-Ig is shown to block tumor development. Taken together, these observations suggest that the tumor growth promoting property of CD44 is largely dependent on its ability to mediate cell attachment to hyaluronate.