PC cell-derived growth factor (granulin precursor) expression and action in human multiple myeloma.
PC cell-derived growth factor (granulin precursor) expression and action in human multiple myeloma.
复制标题
DOI：
--
复制
发表时间：
2003-06
期刊：
影响因子：
--
通讯作者：
Wengang Wang;J. Hayashi;W. Kim;G. Serrero
中科院分区：
文献类型：
--
作者：
Wengang Wang;J. Hayashi;W. Kim;G. Serrero
目的：多发性骨髓瘤（MM）是一种克隆性b细胞肿瘤。PC细胞衍生生长因子（PCDGF）是一种M(r) 88,000糖蛋白生长因子。我们的目的是研究PCDGF在人MM中的表达、功能和信号通路。实验设计使用两种人MM细胞系：ARP-1和RPMI 8226研究PCDGF在人MM中的表达、功能和信号通路。此外，利用13例人骨髓活检样本检测MM患者的PCDGF表达。结果在人MM细胞株ARP-1和RPMI 8226中检测到PCDGF mRNA和蛋白的表达。外源性添加PCDGF对ARP-1和RPMI 8226细胞的生长和持续细胞存活均有剂量依赖性和时间依赖性。相反，中和性抗PCDGF抗体抑制RPMI 8226细胞的生长，表明PCDGF是MM细胞的自分泌生长因子。信号转导通路研究显示PCDGF刺激有丝分裂原激活的蛋白激酶和磷脂酰肌醇3'-激酶通路，但不刺激janus激活的激酶-信号转导和转录激活通路。MM患者骨髓涂片的免疫组织化学分析显示PCDGF表达与MM患者骨髓瘤细胞相关，并与MM疾病的存在相关。结论PCDGF在人MM细胞的生长和存活过程中是一种自分泌生长因子，可能作为MM细胞的生物标志物。
PURPOSE Multiple myeloma (MM) is a clonal B-cell neoplasm. PC cell-derived growth factor (PCDGF) is a M(r) 88,000 glycoprotein growth factor. Our objective was to investigate the expression, function, and signaling pathways of PCDGF in human MM. EXPERIMENTAL DESIGN PCDGF expression, function, and signaling pathways in human MM were studies using two human MM cell lines: ARP-1 and RPMI 8226. In addition, PCDGF expression in MM patients was examined using 13 human bone marrow biopsy samples. RESULTS PCDGF mRNA and protein expression was detected in human MM cell lines such as ARP-1 and RPMI 8226. PCDGF added exogenously stimulated cell growth and sustained cell survival of both ARP-1 and RPMI 8226 cells in a dose- and time-dependent fashion. Conversely, treatment with neutralizing anti-PCDGF antibody inhibited the growth of RPMI 8226 cells suggesting that PCDGF acts as an autocrine growth factor for MM cells. Studies of signal transduction pathways showed PCDGF stimulated mitogen-activated protein kinase and phosphatidylinositol 3'-kinase pathways but not the Janus-activated kinase-signal transducer and activator of transcription pathway. Immunohistochemical analysis of bone marrow smears obtained from MM patients indicated that PCDGF expression was associated with myeloma cells from MM patients and correlated with the presence of MM disease. CONCLUSION These data suggest that PCDGF is an autocrine growth factor in the cell growth and survival of human MM cells, and may be a potential candidate as a biomarker of MM cells.