Inhibition of breast cancer metastasis by selective synthetic polypeptide against CXCR4
Inhibition of breast cancer metastasis by selective synthetic polypeptide against CXCR4
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DOI：
10.1158/0008-5472.can-03-3958
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发表时间：
2004-06-15
期刊：
影响因子：
11.2
通讯作者：
Shim, H
中科院分区：
文献类型：
--
作者：
Liang, ZX;Wu, T;Shim, H
转移与白细胞运输有许多相似之处。在那些被认为参与造血细胞归巢的趋化因子受体中，基质细胞衍生因子-1及其受体CXC趋化因子受体-4（CXCR 4）受到了相当大的关注。与造血细胞归巢一样，基质细胞衍生因子-1在乳腺癌转移部位（包括淋巴结、肺、肝和骨髓）的水平较高。此外，CXCR 4在正常乳腺组织中表达较低，而在恶性肿瘤中表达较高，这表明阻断CXCR 4可能会限制肿瘤转移。因此，我们研究了合成的拮抗剂14-mer肽（TN 14003）在抑制动物模型中的转移的作用。TN 14003不仅可以通过抑制迁移有效限制乳腺癌的转移，而且还可能被证明可用作诊断试剂，用于识别培养物中的CXCR 4受体阳性肿瘤细胞和石蜡包埋临床样本中的肿瘤。
Metastasis shares many similarities with leukocyte trafficking. Among those chemokine receptors thought to be involved in hemopoietic cell homing, stromal cell-derived factor-1 and its receptor CXC chemokine receptor-4 (CXCR4) have received considerable attention. Like hemopoietic cell homing, levels of stromal cell-derived factor-1 are high at sites of breast cancer metastasis including lymph node, lung, liver, and the marrow. Moreover, CXCR4 expression is low in normal breast tissues and high in malignant tumors, suggesting that a blockade of CXCR4 might limit tumor metastasis. We therefore investigated the role of a synthetic antagonist 14-mer peptide (TN14003) in inhibiting metastasis in an animal model. Not only was TN14003 effective in limiting metastasis of breast cancer by inhibiting migration, but it may also prove useful as a diagnostic too] to identify CXCR4 receptor-positive tumor cells in culture and tumors in paraffin-embedded clinical samples.