AUTOREGULATION OF NEUROBLASTOMA GROWTH BY VASOACTIVE-INTESTINAL-PEPTIDE

被引:17
作者
PENCE, JC [1 ]
SHORTER, NA [1 ]
HAASE, G [1 ]
PENCE, JC [1 ]
机构
[1] DUKE UNIV, MED CTR, DEPT SURG, PEDIAT SURG SECT, DURHAM, NC 27710 USA
关键词
NEUROBLASTOMA; VASOACTIVE INTESTINAL PEPTIDE; RETINOIC ACID;
D O I
10.1016/0022-3468(92)90536-G
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Elevated serum levels of vasoactive intestinal peptide (VIP) are associated with some cases of neuroblastoma and correlate with a favorable prognosis. VIP has previously been shown in our laboratory to cause the in vitro growth inhibition and morphological differentiation of the human neuroblastoma cell line, LA-N-5. It is now shown that LA-N-5 cells express immunoreactive VIP and bear specific VIP receptors. Antagonism of endogenous VIP, either by competitive inhibition or receptor blockade, increased cell proliferation, suggesting that VIP is operative in normal growth regulation. Intracellular and extracellular levels of VIP were also shown to increase significantly during the retinoic acid-induced differentiation of these cells. Furthermore, a concomitant marked increase in VIP receptor expression was demonstrated with cellular differentiation. These receptors remain functional as evidenced by a matching increase in the level of detectable cAMP generated in response to exogenous VIP. It is concluded that VIP is a normal autoregulator of neuroblastoma cell growth and differentiation, and that retinoic acid-mediated differentiation may be, in part, due to endogenous VIP. © 1992.
引用
收藏
页码:935 / 944
页数:10
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