Overlapping and distinct role of CXCR7-SDF-1/ITAC and CXCR4-SDF-1 axes in regulating metastatic behavior of human rhabdomyosarcomas.
Overlapping and distinct role of CXCR7-SDF-1/ITAC and CXCR4-SDF-1 axes in regulating metastatic behavior of human rhabdomyosarcomas.
复制标题
DOI：
10.1002/ijc.25245
复制
发表时间：
2010-12-01
影响因子：
6.4
通讯作者：
Ratajczak, Mariusz Z.
中科院分区：
文献类型：
--
作者：
Grymula, Katarzyna;Tarnowski, Maciej;Wysoczynski, Marcin;Drukala, Justyna;Barr, Frederic G.;Ratajczak, Janina;Kucia, Magdalena;Ratajczak, Mariusz Z.
我们已经证明α-趋化因子基质衍生因子（SDF）-1-CXCR 4轴在横纹肌肉瘤（RMS）转移中起重要作用。随着CXCR 7的发现，我们开始对CXCR 7-SDF-1/ITAC轴在RMS进展中的作用感兴趣。为了解决这个问题，我们评估了6个高转移性肺泡（A）RMS和3个低转移性胚胎（E）RMS细胞系，发现所有这些细胞系都表达CXCR 7。虽然CXCR 4在高转移性ARMS系中以高得多的水平表达，但CXCR 7在ERMS系中以高水平存在。我们还注意到RMS细胞上的CXCR 7表达在缺氧条件下下调。更重要的是，RMS细胞系上的CXCR 7受体在用ITAC和SDF-1刺激后是功能性的，如通过促分裂原活化蛋白激酶（MAPK）p42/44和AKT磷酸化以及CXCR 7内化、趋化性、细胞运动性和粘附测定所证明的。与CXCR 4类似，来自活化CXCR 7的信号传导与RMS增殖或细胞存活增加无关。此外，CXCR 7 + RMS细胞在CXCR 4拮抗剂（T140，AMD 3100）存在下对SDF-1和I-TAC有应答。此外，虽然静脉注射过表达CXCR 7的RMS细胞导致肿瘤细胞向骨髓的接种效率增加，但CXCR 7下调显示出相反的效果。总之，CXCR 7-SDF-1/ITAC轴参与RMS的进展;单独靶向CXCR 4-SDF-1轴而不同时阻断CXCR 7将是抑制SDF-1介导的RMS细胞促转移反应的低效策略。
We have demonstrated that the α-chemokine stromal-derived factor (SDF)-1-CXCR4 axis plays an important role in rhabdomyosarcoma (RMS) metastasis. With the recent descriptionof CXCR7, a new receptor for SDF-1 that also binds the interferon-inducible T-cell alpha chemoattractant (ITAC) chemokine, we became interested in the role of the CXCR7-SDF-1/ITAC axis in RMS progression. To address this issue, we evaluated 6 highly metastatic alveolar (A)RMS and 3 less metastatic embryonal (E)RMS cell lines and found that all these cell lines express CXCR7. While CXCR4 was expressed at a much higher level by highly metastatic ARMS lines, CXCR7 was present at a high level on ERMS lines. We also noticed that CXCR7 expression on RMS cells was downregulated in hypoxic conditions. More importantly, the CXCR7 receptor on RMS cell lines was functional after stimulation with ITAC and SDF-1 as evidenced by mitogen-activated protein kinase (MAPK)p42/44 and AKT phosphorylation as well as CXCR7 internalization, chemotaxis, cell motility, and adhesion assays. Similarly to CXCR4, signaling from activated CXCR7 was not associated with increased RMS proliferation or cell survival. Moreover, CXCR7+ RMS cells responded to SDF-1 and I-TAC in the presence of CXCR4 antagonists (T140, AMD3100). Furthermore, while intravenous injection of RMS cells with overexpressed CXCR7 resulted in increased seeding efficiency of tumor cells to bone marrow, CXCR7 downregulation showed the opposite effect. In conclusion, the CXCR7-SDF-1/ITAC axis is involved in the progression of RMS; targeting of the CXCR4-SDF-1 axis alone without simultaneous blockage of CXCR7 will be an inefficient strategy for inhibiting SDF-1-mediated pro-metastatic responses of RMS cells.
登录
查看更多内容
影响因子：
15.3
作者：
Amara, A;LeGall, S;Schwartz, O;Salamero, J;Montes, M;Loetscher, P;Baggiolini, M;Virelizier, JL;ArenzanaSeisdedos, F
通讯作者：
ArenzanaSeisdedos, F
影响因子：
--
作者：
GRULER, H;NUCCITELLI, R
通讯作者：
NUCCITELLI, R
影响因子：
11.4
作者：
Majka, M;Rozmyslowicz, T;Ratajczak, MZ
通讯作者：
Ratajczak, MZ
影响因子：
6.4
作者：
Matsuo, Yoichi;Ochi, Nobuo;Sawai, Hirozumi;Yasuda, Akira;Takahashi, Hiroki;Fumahashi, Hitoshi;Takeyama, Hiromitsu;Tong, Zhimin;Guha, Sushovan
通讯作者：
Guha, Sushovan
影响因子：
6.5
作者：
Janowska-Wieczorek, A;Marquez, LA;Edwards, DR
通讯作者：
Edwards, DR