Iiizumi Megumi, Mohinta Sonia, Bandyopadhyay Sucharita, Watabe Kounosuke
Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, 801 N. Rutledge St., P.O. Box 19626, Springfield, IL 62794-9626, USA.
Microvasc Res. 2007 Sep-Nov;74(2-3):114-20. doi: 10.1016/j.mvr.2007.04.002. Epub 2007 Apr 14.
Metastasis is the primary cause of death in cancer patients. However, the molecular mechanism of the metastatic process is poorly understood because it involves multiple steps with a high degree of complexity. A critical step for successful establishment of secondary colonization is the hematogenous dissemination of malignant cells. During this process, the attachment of cancer cells to the endothelial cells on microvasculature is considered to be an essential step and many adhesion molecules as well as chemokines have been found to be involved in this process. This interaction of cancer-endothelial cell is considered not only to determine the physical site of metastasis, but also to provide the necessary anchorage to facilitate tumor cell extravasation. However, recent evidence indicates that this interaction also serves as a host defense mechanism and hinders the process of metastasis. The tumor metastases suppressor gene, KAI1, has been known to block metastatic process without affecting the primary tumor growth, and this protein has been found to be able to bind to the chemokine receptor, Duffy antigen receptor for chemokines (DARC), which is expressed on endothelial cells. Importantly, this interaction markedly induces senescence of tumor cells. This novel finding is not only significant in the context of molecular dissection of metastatic process but also in the therapeutic implication to develop drugs inhibiting metastasis.
转移是癌症患者死亡的主要原因。然而，转移过程的分子机制却知之甚少，因为它涉及多个高度复杂的步骤。成功建立继发性定植的关键步骤是恶性细胞的血行播散。在此过程中，癌细胞与微脉管系统内皮细胞的黏附被认为是一个关键步骤，并且已发现许多黏附分子和趋化因子都参与了这一过程。这种癌细胞与内皮细胞的相互作用不仅被认为决定了转移的物理部位，还为促进肿瘤细胞外渗提供了必要的锚定。然而，最近的证据表明，这种相互作用也是一种宿主防御机制，会阻碍转移过程。肿瘤转移抑制基因KAI1已知可阻断转移过程而不影响原发肿瘤的生长，并且已发现该蛋白能够与在内皮细胞上表达的趋化因子受体——趋化因子达菲抗原受体（DARC）结合。重要的是，这种相互作用显著诱导肿瘤细胞衰老。这一新发现不仅在转移过程的分子剖析方面具有重要意义，而且在开发抑制转移药物的治疗意义方面也具有重要意义。
