Hou Tianhui, Lou Yan, Li Shichang, Zhao Chenglong, Ji Yingzheng, Wang Dongsheng, Tang Liang, Zhou Ming, Xu Wei, Qian Ming, Wu Zhipeng, Zhao Jian, Wei Haifeng, Li Zhenxi, Xiao Jianru
Key Laboratory of Adolescent Health Assessment and Exercise Intervention, Ministry of Education, School of Physical Education and Health Care, East China Normal University, Shanghai 200241, P.R. China.
Spine Tumor Center, Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
Oncol Lett. 2018 Aug;16(2):2255-2262. doi: 10.3892/ol.2018.8935. Epub 2018 Jun 8.
Breast cancer (BC) is characterized by high incidences of bone metastases. Current treatment strategies for BC bone metastases primarily focused on breaking the 'vicious osteolytic cycle'. Platelet-activating factor (PAF) is a potent phospholipid mediator, which has previously reported biological activities in BC progression and osteoclast differentiation by activating its receptor PAF receptor (PTAFR). However, the role of PAF in the mediation of BC bone metastases remains elusive. In the present study, it was revealed that the upregulation of PTAFR was associated with an increased incidence of bone metastases. It was also revealed that PAF significantly enhanced the processes of BC cell migration and BC mediated osteoclastogenesis. These results suggest that PAF serves a promotion role in BC bone metastases. It was further demonstrated that the natural PAF antagonist Kadsurenone may effectively attenuate each process by partially blocking the PAF/PTAFR signaling pathway. Therefore, targeting PAF/PTAFR by Kadsurenone may be a promising treatment strategy for BC bone metastases.
乳腺癌(BC)的特征是骨转移发生率高。目前针对BC骨转移的治疗策略主要集中在打破“恶性溶骨循环”。血小板活化因子(PAF)是一种强效磷脂介质,此前有报道称其通过激活其受体PAF受体(PTAFR)在BC进展和破骨细胞分化中具有生物学活性。然而,PAF在介导BC骨转移中的作用仍不清楚。在本研究中,发现PTAFR的上调与骨转移发生率增加有关。还发现PAF显著增强了BC细胞迁移和BC介导的破骨细胞生成过程。这些结果表明PAF在BC骨转移中起促进作用。进一步证明,天然PAF拮抗剂海风藤酮可能通过部分阻断PAF/PTAFR信号通路有效减弱每个过程。因此,用海风藤酮靶向PAF/PTAFR可能是一种有前途的BC骨转移治疗策略。