Mitogenesis in glioblastoma multiforme cell lines: A role for NGF and its TrkA receptors
Mitogenesis in glioblastoma multiforme cell lines: A role for NGF and its TrkA receptors
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DOI：
10.1023/a:1006323523437
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发表时间：
1999-10-01
影响因子：
3.9
通讯作者：
Karp, CL
中科院分区：
文献类型：
--
作者：
Singer, HS;Hansen, B;Karp, CL
神经营养因子在神经元群体的生长/维持中具有确定的作用，但其在恶性胶质瘤中的功能尚不清楚。在几种人多形性胶质母细胞瘤（GBM）细胞系（包括U251、U87和U373）中研究了神经生长因子（NGF）作为促有丝分裂剂的能力。在无血清培养基中，向这些细胞系中添加NGF（200 ng/ml）在培养3天后使细胞计数分别比对照增加9%、16%和33%。在更严格研究的U373细胞系中发现细胞计数和[（3）H]胸苷摄取呈剂量依赖性增加。高亲和力的神经生长因子特异性酪氨酸激酶结合位点（p140（TrkA）; TrkA）和低亲和力的神经营养因子（p75（NTR））受体的蛋白质都存在于所有三个GBM细胞系。在U373（仅研究细胞系）中鉴定了TrkA mRNA。NGF刺激的增殖以剂量依赖性方式被Trk诱导的受体激酶阻断剂K252 a抑制。通过ELISA测量，即使在无血清培养基中生长7天后，在所有GBM细胞系中也可检测到NGF。这些数据表明，GBM细胞的生长可以通过NGF通过Trk受体磷酸化作用而增强。未来的抗增殖治疗研究应考虑针对细胞内Trk信号级联的药物。
Neurotrophins have definitive roles in the growth/maintenance of neuronal populations, but their function in malignant gliomas is unknown. The ability for nerve growth factor (NGF) to serve as a mitogenic agent was investigated in several human glioblastoma multiforme (GBM) cell lines, including U251, U87, and U373. In a serum-free medium, the addition of NGF (200 ng/ml) to these cell lines increased cell counts over controls, after 3 days in culture by 9%, 16%, and 33%, respectively. Dose-dependent increases in cell counts and [(3)H]thymidine uptake were found in the more rigorously investigated U373 cell line. Proteins for both the high affinity NGF-specific tyrosine kinase binding site (p140(TrkA); TrkA) and the low affinity neurotrophin (p75(NTR)) receptor were present in all three GBM cell lines. TrkA mRNA was identified in U373 (only cell line studied). NGF-stimulated proliferation was inhibited in a dose-dependent fashion by K252a, a blocker of Trk-induced receptor kinases. NGF, measured by ELISA, was detectable in all GBM cell lines even after 7 days of growth in serum-free medium. These data suggest that GBM cell growth can be enhanced by NGF acting via Trk receptor phosphorylation. Future studies of antiproliferative therapies should consider agents directed against intracellular Trk signaling cascades.