Murakami Takashi, Cardones Adela R, Hwang Sam T
Division of Organ Replacement Research, Center for Molecular Medicine, Jichi Medical School, Tochigi 329-0498, Japan.
J Dermatol Sci. 2004 Nov;36(2):71-8. doi: 10.1016/j.jdermsci.2004.03.002.
Cancer metastasis is the end result of a complex series of biologic events that leads to the formation of clinically significant secondary tumors at distant sites. The sites of distant metastasis are not random since certain tumors show a tendency to develop metastases in specific organs. Human melanoma, for example, demonstrates frequent metastasis to brain, lungs, lymph nodes, and skin. Herein, we review the evidence that suggests that a limited number of chemokine receptors may play critical roles in determining organ-selective metastasis in melanoma by regulating diverse processes such as chemoattraction, adhesion, and survival. In particular, we describe roles for CC chemokine receptor 7 (CCR7) in lymph node metastasis, CXC chemokine receptor 4 (CXCR4) in pulmonary metastasis, and CCR10 in skin metastasis, using a mouse model of melanoma. Preliminary evidence in this preclinical model suggests that inhibiting the function of these receptors may decrease the ability of cancer cells to disseminate to other sites and/or block their ability to survive and form tumors. Therefore, manipulation of the chemokine network could have therapeutic potential in human malignancies.
癌症转移是一系列复杂生物学事件的最终结果，这些事件导致在远处部位形成具有临床意义的继发性肿瘤。远处转移的部位并非随机，因为某些肿瘤显示出在特定器官发生转移的倾向。例如，人类黑色素瘤常转移至脑、肺、淋巴结和皮肤。在此，我们综述了相关证据，这些证据表明有限数量的趋化因子受体可能通过调节诸如化学吸引、黏附和存活等多种过程，在决定黑色素瘤的器官选择性转移中发挥关键作用。特别是，我们利用黑色素瘤小鼠模型描述了CC趋化因子受体7（CCR7）在淋巴结转移中的作用、CXC趋化因子受体4（CXCR4）在肺转移中的作用以及CCR10在皮肤转移中的作用。这个临床前模型的初步证据表明，抑制这些受体的功能可能会降低癌细胞扩散到其他部位的能力和/或阻断其存活及形成肿瘤的能力。因此，操纵趋化因子网络可能对人类恶性肿瘤具有治疗潜力。
