Site-specific metastasis formation Chemokines as regulators of tumor cell adhesion, motility and invasion
Site-specific metastasis formation Chemokines as regulators of tumor cell adhesion, motility and invasion
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DOI：
10.4161/cam.3.4.9211
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发表时间：
2009-10-01
影响因子：
3.2
通讯作者：
Ben-Baruch, Adit
中科院分区：
文献类型：
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作者：
Ben-Baruch, Adit
肿瘤的转移扩散是一个协调良好的过程，其中不同类型的癌症倾向于在限定的器官中形成转移。位点特异性转移的形成需要肿瘤细胞的内在特性与肿瘤微环境之间的完全相容性。近年来研究发现，在特定位点表达的趋化因子促进表达相应受体的肿瘤细胞的粘附、迁移和侵袭。在该家族的不同成员中，CXCL 12趋化因子及其同源CXCR 4受体是该过程的原型，尽管该家族的其他成员（例如CCR 7和CCR 10）也在确定转移性扩散中发挥作用。这篇评论讨论了趋化因子及其受体在位点特异性转移中的基本作用，重点是CXCL 12-CXCR 4。文章还介绍了一些迄今为止，为了确定参与这一过程的细胞内成分进行的努力。重点放在调节肿瘤细胞响应CXCL 12的粘附和迁移的蛋白质所发挥的作用上，主要包括粘着斑激酶（FAK）、Pyk 2/RAFTK和GTP酶的Rho家族成员（RhoA、Rac、Cdc 42）。接下来是讨论在未来的研究中需要解决的开放性问题，以及迄今为止在这一领域的研究结果的潜在治疗意义。
The metastatic spread of tumors is a well-coordinated process in which different types of cancers tend to form metastases in defined organs. The formation of site-specific metastases requires full compatibility between the intrinsic properties of the tumor cells and the tumor microenvironment. It was recently found that chemokines which are expressed in specific loci promote the adhesion, migration and invasion of tumor cells that express the corresponding receptor(s). Of the different members of the family, the CXCL12 chemokine and its cognate CXCR4 receptor are the prototypes of this process, although other members of the family (e.g. CCR7 and CCR10) also play a role in determination of the metastatic spread. This commentary addresses the fundamental roles of chemokines and their receptors in site-specific metastasis, with emphasis on CXCL12-CXCR4. The article also describes some of the efforts that were performed thus far in order to identify the intracellular components involved in this process. The focus is put on the roles played by proteins that regulate adhesion and migration of tumor cells in response to CXCL12, including mainly focal adhesion kinase (FAK), Pyk2/RAFTK and members of the Rho family of GTPases (RhoA, Rac, Cdc42). This is followed by discussion of open questions that need to be addressed in future research, and of the potential therapeutic implications of the findings that are available to date in this field.