流浪肿瘤：三阴性乳腺癌细胞诱饵
当血管破裂时，大量血小板被激活并聚集于出血部位，这对于正常止血至关重要。不过，血小板过度激活也会引起许多可能致命的疾病，例如心肌梗塞、中风、癌症转移。如果对血小板进行改造，使其失去激活和聚集能力，可以成为血小板激活连锁反应的可逆抑制剂。
2019年2月13日，美国科学促进会《科学》旗下《转化医学》封面发表哈佛大学、乔治华盛顿大学、波士顿儿童医院、麻省理工学院、马萨诸塞大学的研究报告，发现血小板替身（又称血小板诱饵）能够防止血栓形成以及癌症转移。
该研究对人类血小板进行洗涤萃取改造，形成血小板替身，保留了血小板的结合能力，但是失去了血小板的激活和聚集能力。虽然现有的抗血小板药物也能抑制血小板激活，但是逆转其作用需要至少一周，这大大增加了创伤或其他致命出血患者的风险。血小板替身作用被逆转的速度，远远快于现有的抗血小板药物。
体外研究表明，血小板替身可以抑制血小板在血栓形成表面发生聚集和黏附，该抑制作用可以通过加入正常新鲜血小板立即逆转。新西兰兔体内研究表明，用血小板替身预先处理，可以抑制动脉损伤诱发的血栓栓塞，该抑制作用可以通过加入正常新鲜血小板立即逆转。
此外，血小板替身还可干扰血小板所致人类三阴性乳腺癌细胞（MDA-MB-231）和激素受体阳性乳腺癌细胞（MCF-7）的聚集，减少人类微血管系统的癌细胞停留和浸润。向实验小鼠体内同时注射血小板替身，可以抑制人类三阴性乳腺癌细胞（MDA-MB-231）转移病灶生长。血小板替身如同诱饵一样，癌细胞被其结合以后，虽然到处流浪，但是无法落地生根形成转移病灶，直至凋亡。
因此，该研究结果表明，血小板替身有望成为抗血栓形成和抗乳腺癌转移的有效方法。
Sci Transl Med. 2019 Feb 13;11(479):eaau5898.
Platelet decoys inhibit thrombosis and prevent metastatic tumor formation in preclinical models.
Anne-laure Papa, Amanda Jiang, Netanel Korin, Michelle B. Chen, Erin T. Langan, Anna Waterhouse, Emma Nash, Jildaz Caroff, Amanda Graveline, Andyna Vernet, Akiko Mammoto, Tadanori Mammoto, Abhishek Jain, Roger D. Kamm, Matthew J. Gounis, Donald E. Ingber.
Harvard University, Boston, MA, USA; The George Washington University, Washington, DC, USA; Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Massachusetts Institute of Technology, Cambridge, MA, USA; University of Massachusetts, Worcester, MA, USA; Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA, USA.
Human platelet decoys prevented thrombosis in rabbits and inhibited cancer cell aggregation and extravasation in vitro and in a mouse model.
DECEIVING PLATELETS
Platelets play a key role in homeostasis; however, platelet activation also contributes to several disorders, including cardiac diseases and cancer. Platelet inhibitors have been developed; however, slow reversal time increases the risk of adverse events. Now, Papa et al. produced rapidly reversible drug-free antiplatelet agents by modifying human platelets. The modified platelets, called platelet decoys, prevented thrombus formation in rabbits. Moreover, platelet decoys decreased metastasis formation in a mouse model of breast cancer by preventing cancer cell extravasation. The results suggest that platelet decoys might be an effective rapidly reversible therapy for treating thrombosis and possibly metastasis formation.
Platelets are crucial for normal hemostasis; however, their hyperactivation also contributes to many potentially lethal pathologies including myocardial infarction, stroke, and cancer. We hypothesized that modified platelets lacking their aggregation and activation capacity could act as reversible inhibitors of platelet activation cascades. Here, we describe the development of detergent-extracted human modified platelets (platelet decoys) that retained platelet binding functions but were incapable of functional activation and aggregation. Platelet decoys inhibited aggregation and adhesion of platelets on thrombogenic surfaces in vitro, which could be immediately reversed by the addition of normal platelets; in vivo in a rabbit model, pretreatment with platelet decoys inhibited arterial injury-induced thromboembolism. Decoys also interfered with platelet-mediated human breast cancer cell aggregation, and their presence decreased cancer cell arrest and extravasation in a microfluidic human microvasculature on a chip. In a mouse model of metastasis, simultaneous injection of the platelet decoys with tumor cells inhibited metastatic tumor growth. Thus, our results suggest that platelet decoys might represent an effective strategy for obtaining antithrombotic and antimetastatic effects.
DOI: 10.1126/scitranslmed.aau5898
以下广告内容与本微信公众号无关