Tang Yu, Qian Cheng, Zhou Yueke, Yu Chang, Song Mengyao, Zhang Teng, Min Xuewen, Wang Aiyun, Zhao Yang, Lu Yin
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
iScience. 2023 Aug 23;26(9):107704. doi: 10.1016/j.isci.2023.107704. eCollection 2023 Sep 15.
Platelets have been widely recognized as a bona fide mediator of malignant diseases, and they play significant roles in influencing various aspects of tumor progression. Paracrine interactions between platelets and tumor cells have been implicated in promoting the dissemination of malignant cells to distant sites. However, the underlying mechanisms of the platelet-tumor cell interactions for promoting hematogenous metastasis are not yet fully understood. We found that activated platelets with high expression of CD36 were prone to release a plethora of growth factors and cytokines, including high levels of PDGF-B, compared to resting platelets. PDGF-B activated the PDGFR-β/COX-2 signaling cascade, which elevated an array of pro-inflammatory factors levels, thereby aggravating tumor metastasis. The collective administration of CD36 inhibitor and COX-2 inhibitor resolved the interactions between platelets and tumor cells. Collectively, our findings demonstrated that targeting the crosstalk between platelets and tumor cells offers potential therapeutic strategies for inhibiting tumor metastasis.
血小板已被广泛认为是恶性疾病的一种真正介质，并且它们在影响肿瘤进展的各个方面发挥着重要作用。血小板与肿瘤细胞之间的旁分泌相互作用与促进恶性细胞向远处转移有关。然而，血小板-肿瘤细胞相互作用促进血行转移的潜在机制尚未完全了解。我们发现，与静息血小板相比，高表达CD36的活化血小板易于释放大量生长因子和细胞因子，包括高水平的血小板源性生长因子-B（PDGF-B）。PDGF-B激活了血小板源性生长因子受体-β（PDGFR-β）/环氧化酶-2（COX-2）信号级联反应，这提高了一系列促炎因子的水平，从而加剧肿瘤转移。CD36抑制剂和COX-2抑制剂的联合给药解决了血小板与肿瘤细胞之间的相互作用。总的来说，我们的研究结果表明，针对血小板与肿瘤细胞之间的相互作用提供了抑制肿瘤转移的潜在治疗策略。
