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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Platelet and osteoclast β_3 integrins are critical for bone metastasis
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Platelet and osteoclast β_3 integrins are critical for bone metastasis

机译：血小板和破骨细胞β_3整合素对骨转移至关重要

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摘要

Mice with a targeted deletion of β_3 integrin were used to examine the process by which tumor cells metastasize and destroy bone. Injection of B16 melanoma cells into the left cardiac ventricle resulted in osteolytic bone metastasis in 74% of β_3~(+/+) mice by 14 days. In contrast, only 4% of β_3~(-/-) mice developed bone lesions. Direct intratibial inoculation of tumor resulted in marrow replacement by tumor in β_3~(-/-) mice, but no associated trabecular bone resorption as seen in β_3(+/+) mice. Bone marrow transplantation studies showed that susceptibility to bone metastasis was conferred by a bone marrow-derived cell. To dissect the roles of osteoclast and platelet β_3 integrins in this model of bone metastasis, osteoclast-defective src~(-/-) mice were used. Src-null mice were protected from tumor-associated bone destruction but were not protected from tumor cell metastasis to bone. In contrast, a highly specific platelet aggregation inhibitor of activated α_(IIb)β_3 prevented B16 metastases. These data demonstrate a critical role for platelet α_(IIb)β_3 in tumor entry into bone and suggest a mechanism by which antiplatelet therapy may be beneficial in preventing the metastasis of solid tumors.
机译：使用靶向性删除β_3整合素的小鼠来检查肿瘤细胞转移和破坏骨骼的过程。到14天时，向左心室注射B16黑色素瘤细胞导致74％的β_3〜（+ / +）小鼠发生溶骨性转移。相比之下，只有4％的β_3〜（-/-）小鼠出现骨病变。直接在胫骨内接种肿瘤可导致β_3〜（-/-）小鼠被骨髓替代，但与β_3（+ / +）小鼠相比无相关的小梁骨吸收。骨髓移植研究表明，骨髓来源的细胞赋予了对骨转移的敏感性。为了剖析破骨细胞和血小板β_3整合素在这种骨转移模型中的作用，使用了破骨细胞缺陷型src〜（-/-）小鼠。 Src-null小鼠受到保护，免受肿瘤相关的骨破坏，但不受肿瘤细胞转移至骨的保护。相反，活化的α_（IIb）β_3的高度特异性血小板凝集抑制剂可预防B16转移。这些数据证明了血小板α_（IIb）β_3在肿瘤进入骨中的关键作用，并提出了抗血小板疗法可能有益于预防实体瘤转移的机制。

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