Platelets Promote Metastasis via Binding Tumor CD97 Leading to Bidirectional Signaling that Coordinates Transendothelial Migration.
Platelets Promote Metastasis via Binding Tumor CD97 Leading to Bidirectional Signaling that Coordinates Transendothelial Migration.
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DOI：
10.1016/j.celrep.2018.03.092
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发表时间：
2018-04-17
期刊：
影响因子：
8.8
通讯作者：
Kelly K
中科院分区：
文献类型：
--
作者：
Ward Y;Lake R;Faraji F;Sperger J;Martin P;Gilliard C;Ku KP;Rodems T;Niles D;Tillman H;Yin J;Hunter K;Sowalsky AG;Lang J;Kelly K
肿瘤细胞启动血小板活化，导致生物活性分子的分泌，从而促进转移。肿瘤上的血小板受体尚未得到很好的表征，导致关于血小板促进转移的知识存在重大空白。我们确定了血小板和肿瘤CD 97之间的直接相互作用，刺激快速的双向信号传导。CD 97是一种粘附G蛋白偶联受体（GPCR），是几种癌症类型中过表达的肿瘤抗原。纯化的CD 97胞外结构域或肿瘤细胞相关的CD 97刺激血小板活化。CD 97启动的血小板活化导致颗粒分泌，包括释放ATP，一种内皮连接破坏的介质。来源于血小板的溶血磷脂酸（LPA）通过近端CD 97-LPAR异二聚体信号传导诱导肿瘤侵袭，耦合同时发生的肿瘤细胞迁移和血管通透性以促进跨内皮迁移。与此一致，CD 97是肿瘤细胞诱导的体内血管通透性和临床前模型中转移形成所必需的。这些发现支持靶向阻断肿瘤CD 97作为改善转移扩散的方法。肿瘤引发的血小板活化促进癌细胞的组织侵袭和转移。Ward等人证明，常见的肿瘤相关抗原CD 97导致血小板活化，并直接参与导致肿瘤细胞侵袭的LPA介导的信号转导。CD 97在临床前模型中促进血管外渗和转移。
Tumor cells initiate platelet activation leading to the secretion of bioactive molecules, which promote metastasis. Platelet receptors on tumors have not been well-characterized, resulting in a critical gap in knowledge concerning platelet-promoted metastasis. We identify a direct interaction between platelets and tumor CD97 that stimulates rapid bidirectional signaling. CD97, an adhesion G protein-coupled receptor (GPCR), is an overexpressed tumor antigen in several cancer types. Purified CD97 extra-cellular domain or tumor cell-associated CD97 stimulated platelet activation. CD97-initiated platelet activation led to granule secretion, including the release of ATP, a mediator of endothelial junction disruption. Lysophosphatidic acid (LPA) derived from platelets induced tumor invasiveness via proximal CD97-LPAR heterodimer signaling, coupling coincident tumor cell migration and vascular permeability to promote transendothelial migration. Consistent with this, CD97 was necessary for tumor cell-induced vascular permeability in vivo and metastasis formation in preclinical models. These findings support targeted blockade of tumor CD97 as an approach to ameliorate metastatic spread. Tumor-initiated platelet activation promotes tissue invasion of cancer cells and metastasis. Ward et al. demonstrate that a common tumor-associated antigen, CD97, accounts for platelet activation and participates directly in LPA-mediated signal transduction leading to tumor cell invasion. CD97 promotes vascular extravasation and metastasis in pre-clinical models.
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DOI：
10.1073/pnas.94.19.10098
发表时间：
1997-09-16
影响因子：
11.1
作者：
Fromm, C;Coso, OA;Gutkind, JS
通讯作者：
Gutkind, JS
影响因子：
16.2
作者：
Petersen, Sarah C.;Luo, Rong;Liebscher, Ines;Giera, Stefanie;Jeong, Sung-Jin;Mogha, Amit;Ghidinelli, Monica;Feltri, M. Laura;Schoeneberg, Torsten;Piao, Xianhua;Monk, Kelly R.
通讯作者：
Monk, Kelly R.
CD97小异构体在胃癌中的侵袭和转移促进作用
影响因子：
3.7
作者：
Liu D;Trojanowicz B;Ye L;Li C;Zhang L;Li X;Li G;Zheng Y;Chen L
通讯作者：
Chen L
DOI：
10.1073/pnas.61.1.46
发表时间：
1968-01-01
影响因子：
11.1
作者：
GASIC, GJ;GASIC, TB;STEWART, CC
通讯作者：
STEWART, CC
影响因子：
--
作者：
Jaspars, LH;Vos, W;Hamann, J
通讯作者：
Hamann, J