文章：

布鲁顿酪氨酸激酶（BTK）在INA6骨髓瘤细胞生长和转移中的作用

Role of Bruton’s tyrosine kinase (BTK) in growth and metastasis of INA6 myeloma cells

原文发布日期：2014-08-01

DOI: 10.1038/bcj.2014.54

类型: Original Article

开放获取: 是

英文摘要：

Bruton’s tyrosine kinase (BTK) and the chemokine receptor CXCR4 are linked in various hematologic malignancies. The aim of the study was to understand the role of BTK in myeloma cell growth and metastasis using the stably BTK knockdown luciferase-expressing INA6 myeloma line. BTK knockdown had reduced adhesion to stroma and migration of myeloma cells toward stromal cell-derived factor-1. BTK knockdown had no effect on short-term in vitro growth of myeloma cells, although clonogenicity was inhibited and myeloma cell growth was promoted in coculture with osteoclasts. In severe combined immunodeficient-rab mice with contralaterally implanted pieces of bones, BTK knockdown in myeloma cells promoted their proliferation and growth in the primary bone but suppressed metastasis to the contralateral bone. BTK knockdown myeloma cells had altered the expression of genes associated with adhesion and proliferation and increased mammalian target of rapamycin signaling. In 176 paired clinical samples, BTK and CXCR4 expression was lower in myeloma cells purified from a focal lesion than from a random site. BTK expression in random-site samples was correlated with proportions of myeloma cells expressing cell surface CXCR4. Our findings highlight intratumoral heterogeneity of myeloma cells in the bone marrow microenvironment and suggest that BTK is involved in determining proliferative, quiescent or metastatic phenotypes of myeloma cells.

摘要翻译： 

布鲁顿酪氨酸激酶（BTK）与趋化因子受体CXCR4在多种血液恶性肿瘤中存在关联。本研究旨在通过稳定敲除BTK的荧光素酶表达INA6骨髓瘤细胞系，探讨BTK在骨髓瘤细胞生长和转移中的作用。BTK敲除后，骨髓瘤细胞对基质细胞的粘附能力减弱，并向基质细胞衍生因子-1的迁移减少。尽管BTK敲除对骨髓瘤细胞的短期体外生长无影响，但克隆形成能力受到抑制，且在与破骨细胞共培养时促进了骨髓瘤细胞的生长。在对侧植入骨片的严重联合免疫缺陷-rab小鼠模型中，BTK敲除的骨髓瘤细胞在原发性骨骼中增殖生长增强，但向对侧骨骼的转移受到抑制。BTK敲除的骨髓瘤细胞改变了与粘附和增殖相关基因的表达，并增强了哺乳动物雷帕霉素靶蛋白信号通路。在176对临床样本中，从局灶性病灶纯化的骨髓瘤细胞BTK和CXCR4表达低于随机取样部位。随机取样样本中BTK的表达与细胞表面CXCR4表达的骨髓瘤细胞比例相关。我们的研究结果揭示了骨髓瘤细胞在骨髓微环境中的瘤内异质性，并表明BTK参与决定骨髓瘤细胞的增殖、静息或转移表型。

原文链接：

Role of Bruton’s tyrosine kinase (BTK) in growth and metastasis of INA6 myeloma cells