Metastasis is the main cause of death in cancer patients; there is currently no effective treatment for cancer metastasis. This is primarily due to our insufficient understanding of the metastatic mechanisms in cancer. An increasing number of studies have shown that the C-X-C motif chemokine Ligand 12 (CXCL12) is overexpressed in various tissues and organs. It is a key niche factor that nurtures the pre-metastatic niches (tumorigenic soil) and recruits tumor cells (oncogenic “seeds”) to these niches, thereby fostering cancer cell aggression and metastatic capabilities. However, the C-X-C motif chemokine Receptor 4 (CXCR4) is aberrantly overexpressed in various cancer stem/progenitor cells and functions as a CXCL12 receptor. CXCL12 activates CXCR4 as well as multiple downstream multiple tumorigenic signaling pathways, promoting the expression of various oncogenes. Activation of the CXCL12-CXCR4 signaling axis promotes Epithelial-Mesenchymal Transition (EMT) and mobilization of cancer stem/progenitor cells to pre-metastatic niches. It also nurtures cancer cells with high motility, invasion, and dissemination phenotypes, thereby escalating multiple proximal or distal cancer metastasis; this results in poor patient prognosis. Based on this evidence, recent studies have explored either CXCL12- or CXCR4-targeted anti-cancer therapeutics and have achieved promising results in the preclinical trials. Further exploration of this new strategy and its potent therapeutics effect against metastatic cancer through the targeting of the CXCL12- CXCR4 signaling axis may lead to a novel therapy that can clean up the tumor microenvironment (“soil”) and kill the cancer cells, particularly the cancer stem/progenitor cells (“seeds”), in cancer patients. Ultimately, this approach has the potential to effectively treat metastatic cancer.

转移是癌症患者死亡的主要原因；目前尚无有效的癌症转移治疗方法。这主要是由于我们对癌症转移机制的了解不足。越来越多的研究表明，CXC基序趋化因子配体12（CXCL12）在各种组织和器官中均过表达。它是一个重要的利基因素，可以培育转移前的生态位（致瘤土壤），并将肿瘤细胞（致癌的“种子”）募集到这些生态位，从而促进癌细胞的侵袭和转移能力。但是，CXC基序趋化因子受体4（CXCR4）在各种癌症干/祖细胞中异常过表达，并充当CXCL12受体。CXCL12激活CXCR4以及多个下游多个致瘤信号通路，促进各种癌基因的表达。CXCL12-CXCR4信号轴的激活促进上皮-间充质转化（EMT），并使癌症干/祖细胞动员至转移前的生态位。它还可以培养具有高运动性，侵袭性和扩散表型的癌细胞，从而加剧多发性近端或远端癌转移。这导致患者预后不良。基于这一证据，最近的研究探索了靶向CXCL12或CXCR4的抗癌疗法，并在临床前试验中取得了可喜的结果。通过靶向CXCL12-CXCR4信号轴，进一步探索这一新策略及其对转移性癌症的有效治疗作用，可能会导致一种新颖的疗法，可以清除肿瘤微环境（“土壤”）并杀死癌细胞，尤其是癌症患者的癌症干/祖细胞（“种子”）。最终，这种方法具有有效治疗转移性癌症的潜力。