层粘连蛋白
医学
整合素
中枢神经系统
蛛网膜下腔
骨髓
癌症研究
脑脊液
病理
免疫学
细胞生物学
细胞外基质
受体
生物
内科学
出处
期刊:PubMed
日期:2019-01-01
卷期号:60 (9): 1212-1220
标识
DOI:10.11406/rinketsu.60.1212
摘要
It is well known that acute lymphoblastic leukemia (ALL) cells can invade the central nervous system (CNS), but the underlying mechanism of such invasion is still unclear. We discovered the direct routes taken by ALL cells when migrating into CNS in ALL model mice. We observed that ALL cells migrate along the external surface of vessels that pass directly between the vertebral or calvarial bone marrow and the subarachnoid space. The basement membrane of these bridging vessels is enriched in laminin. The laminin is recognized by integrin α6, which is expressed by ALL cells. The interaction between integrin α6 and laminin mediated the invasion of ALL cells. Furthermore, the expression of integrin α6 depends on PI3Kδ activity. Mice with ALL xenografts were treated with a PI3Kδ inhibitor, which decreased integrin α6 expression on ALL cells. This resulted in significant reductions in blast counts in the cerebrospinal fluid and in CNS disease symptoms. Our data suggest that the PI3Kδ inhibitor has potential to prevent CNS involvement in ALL.
科研通智能强力驱动
Strongly Powered by AbleSci AI