除了在保持血管完整性方面的基本作用外，血小板还有助于肿瘤血管生成和转移。然而，尽管血小板是血管生成和转移性细胞因子的储存库，但它也具有肿瘤进展的负调节因子。 Angpt1（血管生成素-1）是一种对于发育性血管生成至关重要的细胞因子，还可以通过一种未明确的机制防止肿瘤细胞转移。尽管活化的血小板将 Angpt1 从 α 颗粒释放到循环中，但血小板 Angpt1 对肿瘤生长、血管生成和转移的贡献尚未得到研究。使用细胞因子阵列和 ELISA，我们首先比较了乳腺癌和黑色素瘤小鼠肿瘤模型中的血小板 Angpt1 水平，无肿瘤对照。然后，我们评估了缺乏巨核细胞和血小板 Angpt1 (Angpt1Plt KO) 的小鼠的肿瘤生长和转移。使用 RT-PCR 定量乳腺注射肿瘤细胞向肺部的自发转移。使用荧光显微镜和流式细胞术测定静脉注射肿瘤细胞的肺部定植和肿瘤细胞外渗。PyMT（多瘤中间肿瘤抗原）乳腺癌小鼠模型中血小板Angpt1选择性上调，血小板是血液中Angpt1的主要来源循环。虽然原发性肿瘤生长和血管生成不受影响，但 Angpt1Plt KO 小鼠在乳腺或静脉注射后自发性肺转移和肿瘤细胞肺部定植均增加。尽管血小板 Angpt1 不影响肺部最初的肿瘤细胞截留，但 Angpt1Plt KO 小鼠的肿瘤细胞滞留和外渗增加。与对照小鼠 (Angpt1WT) 的血清相比，Angpt1Plt KO 小鼠的血清增加了内皮通透性，降低了内皮连接处的 VE-钙粘蛋白表达。血小板提供了 Angpt1 的血管内来源，通过保留肺微脉管系统限制肿瘤细胞外渗来抑制肿瘤转移。

In addition to their fundamental roles in preserving vascular integrity, platelets also contribute to tumor angiogenesis and metastasis. However, despite being a reservoir for angiogenic and metastatic cytokines, platelets also harbor negative regulators of tumor progression. Angpt1 (angiopoietin-1) is a cytokine essential for developmental angiogenesis that also protects against tumor cell metastasis through an undefined mechanism. Although activated platelets release Angpt1 from α-granules into circulation, the contributions of platelet Angpt1 to tumor growth, angiogenesis, and metastasis have not been investigated.Using cytokine arrays and ELISAs, we first compared platelet Angpt1 levels in breast and melanoma mouse tumor models to tumor-free controls. We then assessed tumor growth and metastasis in mice lacking megakaryocyte and platelet Angpt1 (Angpt1Plt KO). The spontaneous metastasis of mammary-injected tumor cells to the lungs was quantified using RT-PCR. The lung colonization of intravenously injected tumor cells and tumor cell extravasation were determined using fluorescent microscopy and flow cytometry.Platelet Angpt1 is selectively upregulated in the PyMT (polyoma middle tumor antigen) breast cancer mouse model, and platelets are the principal source of Angpt1 in blood circulation. While primary tumor growth and angiogenesis were unaffected, Angpt1Plt KO mice had both increased spontaneous lung metastasis and tumor cell lung colonization following mammary or intravenous injection, respectively. Although platelet Angpt1 did not affect initial tumor cell entrapment in the lungs, Angpt1Plt KO mice had increased tumor cell retention and extravasation. Serum from Angpt1Plt KO mice increased endothelial permeability and reduced VE-cadherin expression at endothelial junctions compared with serum from control mice (Angpt1WT).Platelets provide an intravascular source of Angpt1 that restrains tumor metastasis by preserving the lung microvasculature to limit tumor cell extravasation.