Soluble L1CAM promotes breast cancer cell adhesion and migration in vitro, but not invasion.
Soluble L1CAM promotes breast cancer cell adhesion and migration in vitro, but not invasion.
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DOI：
10.1186/1475-2867-10-34
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发表时间：
2010-09-15
影响因子：
5.8
通讯作者：
Galileo DS
中科院分区：
文献类型：
--
作者：
Li Y;Galileo DS
神经识别分子L1CAM是一种参与早期神经系统发育的关键蛋白，已知在几种癌症中异常表达和脱落，并参与转移和进展。癌组织与正常组织中L1CAM存在的差异表明它是癌症治疗的一个新靶点。我们目前的研究重点是可溶性L1CAM在乳腺癌细胞与细胞外基质蛋白的黏附、迁移和侵袭中的潜在作用。
我们发现，在已建立的临床样本数据集中，L1的表达水平与乳腺癌的进展阶段相关，在更具转移性的乳腺癌细胞系MDA - MB - 231和MDA - MB - 435中较高，而在迁移性较弱的MDA - MB - 468细胞中较低。在上述所有三种细胞系的细胞培养基中都检测到L1被蛋白水解为其可溶性形式（sL1），并且可由佛波醇酯（PMA）激活诱导。通过使用慢病毒载体在MDA - MB - 468细胞中过表达L1胞外域，大大增加了这些细胞释放的sL1的量。同时，细胞与细胞外基质的黏附以及细胞的迁移能力显著增强，而通过基质胶（Matrigel™）的细胞侵袭能力未受影响。另一方面，通过使用短发夹RNA（shRNA）慢病毒载体降低MDA - MB - 231细胞中的L1表达，导致细胞 - 基质黏附和迁移减少。单克隆抗体阻断L1胞外区域也显示出类似的效果。此外，条件培养基中的sL1诱导了MDA - MB - 468细胞的定向迁移，这种迁移可通过抗体处理被中和。
我们的数据为L1CAM及其可溶性形式在促进癌细胞与细胞外基质的黏附以及细胞迁移方面的功能提供了新的证据。因此，进一步证实L1CAM是乳腺癌进展中潜在的早期诊断标志物以及乳腺癌治疗的一个靶点。
Neural recognition molecule L1CAM, which is a key protein involved in early nervous system development, is known to be abnormally expressed and shed in several types of cancers where it participates in metastasis and progression. The distinction of L1CAM presence in cancerous vs. normal tissues has suggested it to be a new target for cancer treatment. Our current study focused on the potential role of soluble L1CAM in breast cancer cell adhesion to extracellular matrix proteins, migration, and invasion. We found L1 expression levels were correlated with breast cancer stage of progression in established data sets of clinical samples, and also were high in more metastatic breast cancer cell lines MDA-MB-231 and MDA-MB-435, but low in less migratory MDA-MB-468 cells. Proteolysis of L1 into its soluble form (sL1) was detected in cell culture medium from all three above cell lines, and can be induced by PMA activation. Over-expression of the L1 ectodomain in MDA-MB-468 cells by using a lentiviral vector greatly increased the amount of sL1 released by those cells. Concomitantly, cell adhesion to extracellular matrix and cell transmigration ability were significantly promoted, while cell invasion ability through Matrigel™ remained unaffected. On the other hand, attenuating L1 expression in MDA-MB-231 cells by using a shRNA lentiviral vector resulted in reduced cell-matrix adhesion and transmigration. Similar effects were also shown by monoclonal antibody blocking of the L1 extracellular region. Moreover, sL1 in conditioned cell culture medium induced a directional migration of MDA-MB-468 cells, which could be neutralized by antibody treatment. Our data provides new evidence for the function of L1CAM and its soluble form in promoting cancer cell adhesion to ECM and cell migration. Thus, L1CAM is validated further to be a potential early diagnostic marker in breast cancer progression and a target for breast cancer therapy.
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影响因子：
4.8
作者：
Kalus, I;Schnegelsberg, B;Schachner, M
通讯作者：
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影响因子：
6.1
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Smith, SB
影响因子：
3.3
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影响因子：
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Yoshihara, F