CD24 expression causes the acquisition of multiple cellular properties associated with tumor growth and metastasis

CD24 expression causes the acquisition of multiple cellular properties associated with tumor growth and metastasis
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DOI:
10.1158/0008-5472.can-05-0619
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发表时间:
2005-12-01
期刊:
影响因子:
11.2
通讯作者:
Sleeman, JP
Sleeman, JP
中科院分区:
医学1区
文献类型:
--
作者:
Baumann, P;Cremers, N;Sleeman, JP

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糖基磷脂酰肌醇锚定膜蛋白CD24作为p -选择素和L1的粘附分子,在b细胞发育和神经发生中起作用。在过去的几年里,大量的文献也表明CD24表达与肿瘤的发生和发展有关。本研究表明,在实验动物中,异位CD24表达足以促进肿瘤转移。通过在乳腺癌细胞中建立强力霉素诱导的CD24表达系统,我们还分析了CD24表达影响的细胞特性。我们发现CD24的表达增加了肿瘤细胞的增殖。此外,除了促进与p -选择素的结合外,CD24的表达还通过激活α (3) β(1)和α (4) β(1)整合素活性间接刺激细胞与纤维连接蛋白、胶原I和胶原IV以及层粘连蛋白的粘附。此外,CD24的表达支持细胞快速扩散,并强烈诱导细胞运动和侵袭。cd24诱导的增殖和运动不依赖于整合素。总之,这些观察结果暗示CD24参与了与肿瘤生长和转移直接相关的多种细胞特性的调节。[j] .癌症杂志,2005;65(23):10783-93。
The glycosylphosphatidylinositol-anchored membrane protein CD24 functions as an adhesion molecule for P-selectin and L1 and plays a role in B-cell development and neurogenesis. Over the last few years, a large body of literature has also implicated CD24 expression in tumorigenesis and progression. Here, we show that ectopic CD24 expression can be sufficient to promote tumor metastasis in experimental animals. By developing a doxycycline-inducible system for the expression of CD24 in breast cancer cells, we have also analyzed the cellular properties that CD24 expression influences. We found that CD24 expression increased tumor cell proliferation. Furthermore, in addition to promoting binding to P-selectin, CD24 expression also indirectly stimulated cell adhesion to fibronectin, collagens I and IV, and laminin through the activation of alpha(3)beta(1) and alpha(4)beta(1) integrin activity. Moreover, CD24 expression supported rapid cell spreading and strongly induced cell motility and invasion. CD24-induced proliferation and motility were integrin independent. Together, these observations implicate CD24 in the regulation of multiple cell properties of direct relevance to tumor growth and metastasis. (Cancer Res 2005; 65(23): 10783-93).