Department of Neurosurgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Mol Carcinog. 2020 Apr;59(4):390-398. doi: 10.1002/mc.23161. Epub 2020 Feb 9.
Brain metastasis is a leading cause of death worldwide, but the mechanism involved remains unclear. Stromal cell-derived factor-1 (SDF-1)/C-X-C motif chemokine receptor 4 (CXCR4) signaling has been reported to induce the directed metastasis of cancers, and adenosine A2A receptor activation suppresses the SDF-1/CXCR4 interaction. However, whether A2A receptor activation implicates the SDF-1/CXCR4 signaling pathway and thus modulates brain metastasis remains unclear. In this study, Western blot was performed to evaluate the protein levels. Cell invasion and migration assays were used to estimate the metastasis ability of PC-9 cells. The viability of cells was demonstrated by lactate dehydrogenase and cell proliferation assays. And the findings in vitro were further identified in nude mice. Notably, adenosine A2A receptor activation inhibited the proliferation and viability of PC-9 cells and thus suppressed the brain metastasis. A2A receptor stimulation protected the function of blood-brain barrier (BBB). The suppression of brain metastasis and the protection of BBB by A2A receptor relied on SDF-1/CXCR4 signaling, and treatment using A2A receptor agonist and CXCR4 antagonist protected the nude mice from malignancy metastasis in vivo. Adenosine A2A receptor activation suppressed the brain metastasis by implicating the SDF-1/CXCR4 axis and protecting the BBB.
脑转移是全球范围内导致死亡的主要原因，但涉及的机制仍不清楚。据报道，基质细胞衍生因子-1 (SDF-1)/C-X-C 趋化因子受体 4 (CXCR4) 信号转导可诱导癌症的定向转移，而腺苷 A2A 受体的激活可抑制 SDF-1/CXCR4 相互作用。然而，A2A 受体的激活是否涉及 SDF-1/CXCR4 信号通路，从而调节脑转移尚不清楚。在本研究中，通过 Western blot 评估蛋白水平。通过细胞侵袭和迁移实验来评估 PC-9 细胞的转移能力。通过乳酸脱氢酶和细胞增殖实验来证明细胞的活力。并在裸鼠中进一步鉴定了体外研究结果。值得注意的是，A2A 受体的激活抑制了 PC-9 细胞的增殖和活力，从而抑制了脑转移。A2A 受体的刺激保护了血脑屏障 (BBB) 的功能。A2A 受体对脑转移的抑制和 BBB 的保护依赖于 SDF-1/CXCR4 信号，使用 A2A 受体激动剂和 CXCR4 拮抗剂治疗可保护裸鼠免受体内恶性转移。A2A 受体的激活通过涉及 SDF-1/CXCR4 轴和保护 BBB 来抑制脑转移。
