旁分泌信号
间质细胞
自分泌信号
内海
癌症研究
生物
细胞生物学
血管内皮生长因子A
血管内皮生长因子
生长因子
受体
生物化学
血管内皮生长因子受体
作者
Loı̈c Vincent,David Jin,Matthias A. Karajannis,Koji Shido,Andrea T. Hooper,William K. Rashbaum,Bronislaw Pytowski,Yan Wu,Daniel J. Hicklin,Zhenping Zhu,Peter Böhlen,Rubén Niesvizky,Shahin Rafii
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2005-04-15
卷期号:65 (8): 3185-3192
被引量:58
标识
DOI:10.1158/0008-5472.can-04-3598
摘要
Induction of neoangiogenesis plays an important role in the pathogenesis of multiple myeloma. However, the mechanism by which expression of vascular endothelial growth factor (VEGF)-A and its receptors modulate the interaction of multiple myeloma cells with stromal cells is not known. Here, we describe a novel in vitro coculture system using fetal bone stromal cells as a feeder layer, which facilitates the survival and growth of human primary multiple myeloma cells. We show that stromal-dependent paracrine VEGF-A signaling promotes proliferation of human primary multiple myeloma cells. Primary multiple myeloma cells only expressed functional VEGF receptor (VEGFR)-1, but not VEGFR-2 or VEGFR-3. VEGFR-1 expression was detected in the cytoplasm and the nuclei of proliferating multiple myeloma cells. Inhibition of VEGFR-1 abrogated multiple myeloma cell proliferation and motility, suggesting that the functional interaction of VEGF-A with its cognate receptor is essential for the growth of primary multiple myeloma cells. Collectively, our results suggest that stromal-dependent paracrine and intracrine VEGF-A/VEGFR-1 signaling contributes to human primary multiple myeloma cell growth and therefore, VEGFR-1 blockade is a potential therapeutic strategy for the treatment of multiple myeloma.
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