CXCL12-CXCR4 Axis Promotes Proliferation, Migration, Invasion, and Metastasis of Ovarian Cancer.
CXCL12-CXCR4 Axis Promotes Proliferation, Migration, Invasion, and Metastasis of Ovarian Cancer.
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DOI：
10.3727/096504015x14343704124430
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发表时间：
2014
影响因子：
3.1
通讯作者：
Wu XH
中科院分区：
文献类型：
--
作者：
Guo Q;Gao BL;Zhang XJ;Liu GC;Xu F;Fan QY;Zhang SJ;Yang B;Wu XH
CXCL12-CXCR4趋化因子轴可能在体内外卵巢癌细胞的增殖、迁移、侵袭和腹膜转移中发挥非常重要的作用。本研究在体外培养转染的SKOV3-CXCR4、转染载体SKOV3阴性、未转染的SKOV3卵巢癌细胞和人腹膜间皮细胞（HPMC），并研究这些卵巢癌细胞在有或没有CXCL12-CXCR4轴的影响下的增殖、迁移和侵袭。通过将卵巢癌细胞注射到腹腔中来创建卵巢癌裸鼠模型，以研究卵巢癌细胞的转移。我们的结果表明，在 SKOV3-CXCR4 组中，用 CXCL12 处理的增殖、迁移或穿透基质胶膜的细胞数显着（p< 0.05）多于用 CXCR4 抗体或 CXCR4 拮抗剂 AMD 3100 处理的细胞数，且呈浓度依赖性。在SKOV3阴性组和未转染SKOV3组中，增殖、迁移或渗透的细胞数量不存在显着（p>0.05）差异。 HPMC 和 SKOV3-CXCR4 共培养的迁移和侵袭率显着高于仅 SKOV3-CXCR4 组（p< 0.05）。在接种卵巢癌细胞的裸鼠中，注射SKOV3-CXCR4细胞的裸鼠的肿瘤重量显着(p<0.05)大于注射SKOV3阴性或未转染SKOV3细胞的裸鼠组。综上所述，我们的研究结果表明CXCL12-CXCR4趋化因子轴可以显着促进卵巢癌细胞的增殖、迁移、侵袭和腹膜转移，干扰该轴可能成为治疗卵巢癌的新治疗靶点。
The CXCL12-CXCR4 chemokine axis may play a very important role in ovarian cancer cells proliferation, migration, invasion, and peritoneal metastasis in vitro and in vivo. In this study, transfected SKOV3-CXCR4, transfected vector SKOV3-negative, nontransfected SKOV3 ovarian cancer cells, and human peritoneal mesothelial cells (HPMCs) were cultivated in vitro, and the proliferation, migration, and invasion of these ovarian cancer cells were investigated with or without the influence of the CXCL12-CXCR4 axis. Nude mice models of ovarian cancer were created by injection of ovarian cancer cells into the peritoneal cavity for investigation of ovarian cancer cells metastasis. Our results demonstrated that in the SKOV3-CXCR4 group, the cell number of proliferation, migration, or penetration through the Matrigel membrane treated with CXCL12 was significantly (p < 0.05) greater than those treated with CXCR4 antibody or CXCR4 antagonist AMD 3100 in a concentration-dependent manner. In the SKOV3-negative and the nontransfected SKOV3 groups, no significant (p > 0.05) differences existed in the cell number of proliferation, migration, or penetration. Coculture of HPMCs and SKOV3-CXCR4 had significantly (p < 0.05) higher migration and invasion rates than the SKOV3-CXCR4-only group. In nude mice seeded with ovarian cancer cells, the tumor weight in the nude mice injected with SKOV3-CXCR4 cells was significantly (p < 0.05) greater than in the group injected with the SKOV3-negative or nontransfected SKOV3 cells. Taken together, our results show that the CXCL12-CXCR4 chemokine axis can significantly promote the proliferation, migration, invasion, and peritoneal metastasis of ovarian cancer cells, and interference with this axis may serve as a new therapeutic target in treating ovarian cancers.