Shanghai Bone Cancer Institute, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
Int J Mol Med. 2013 Dec;32(6):1239-46. doi: 10.3892/ijmm.2013.1521. Epub 2013 Oct 11.
Bone sarcomas, which comprise less than 1% of all human malignancies, are a group of relatively rare mesenchymal-derived tumors. They are mainly composed of osteosarcoma, chondrosarcoma and Ewing's sarcoma. In spite of advances in adjuvant chemotherapy and wide surgical resection, prognosis remains poor due to the high propensity for lung metastasis, which is the leading cause of mortality in patients with bone sarcomas. Chemokines are a superfamily of small pro-inflammatory chemoattractant cytokines which can bind to specific G protein-coupled seven-span transmembrane receptors. Chemokine 12 (CXCL12), also designated as stromal cell-derived factor-1 (SDF-1), is able to bind to its cognate receptors, chemokine receptor 4 (CXCR4) and chemokine receptor 7 (CXCR7), with high affinity. The binding of CXCL12 to CXCR4/CXCR7 stimulates the activation of several downstream signaling pathways that regulate tumor progression and metastasis. In this review, the structure and function of CXCL12 and its receptors, CXCR4 and CXCR7, as well as many factors affecting their expression are discussed. Phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways are the two most important downstream pathways regulated by the CXCL12-CXCR4/CXCR7 interaction. CXCR4 expression in bone sarcomas, including tumor cells and samples and the correlation between CXCR4/CXCR7 expression and the survival of patients with bone sarcomas are also discussed. In addition, we review the involvement of the CXCL12‑CXCR4/CXCR7 axis in the growth and metastasis of bone sarcomas and the targeting of this axis in preclinical studies.
骨肉瘤占人类所有恶性肿瘤的不到 1%，是一组相对罕见的间充质来源的肿瘤。它们主要由骨肉瘤、软骨肉瘤和尤因肉瘤组成。尽管辅助化疗和广泛的手术切除取得了进展，但由于肺转移的高倾向，预后仍然很差，肺转移是导致骨肉瘤患者死亡的主要原因。趋化因子是一个小的促炎趋化细胞因子的超家族，可以与特定的 G 蛋白偶联七跨膜受体结合。趋化因子 12（CXCL12），也称为基质细胞衍生因子 1（SDF-1），能够与它的同源受体趋化因子受体 4（CXCR4）和趋化因子受体 7（CXCR7）高亲和力结合。CXCL12 与 CXCR4/CXCR7 的结合刺激了几个下游信号通路的激活，这些信号通路调节肿瘤的进展和转移。在这篇综述中，讨论了 CXCL12 及其受体 CXCR4 和 CXCR7 的结构和功能，以及影响它们表达的许多因素。磷酸肌醇 3-激酶（PI3K）和丝裂原活化蛋白激酶（MAPK）途径是由 CXCL12-CXCR4/CXCR7 相互作用调节的两个最重要的下游途径。还讨论了骨肉瘤中 CXCR4 的表达，包括肿瘤细胞和样本，以及 CXCR4/CXCR7 表达与骨肉瘤患者生存的相关性。此外，我们回顾了 CXCL12-CXCR4/CXCR7 轴在骨肉瘤生长和转移中的参与，以及该轴在临床前研究中的靶向作用。
