期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：24
页码：14205-14210
DOI：10.1073/pnas.2234372100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Mice with a targeted deletion of {beta}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 {beta}3+/+ mice by 14 days. In contrast, only 4% of {beta}3-/- mice developed bone lesions. Direct intratibial inoculation of tumor resulted in marrow replacement by tumor in {beta}3-/- mice, but no associated trabecular bone resorption as seen in{beta}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 {beta}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 IIb{beta}3 prevented B16 metastases. These data demonstrate a critical role for platelet IIb{beta}3 in tumor entry into bone and suggest a mechanism by which antiplatelet therapy may be beneficial in preventing the metastasis of solid tumors.
