Pence J C, Shorter N A
Department of Surgery, Duke University Medical Center, Durham, NC.
J Pediatr Surg. 1992 Aug;27(8):935-43; discussion 944. doi: 10.1016/0022-3468(92)90536-g.
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.
血清中血管活性肠肽（VIP）水平升高与某些神经母细胞瘤病例相关，且与良好的预后相关。此前在我们实验室已表明，VIP可导致人神经母细胞瘤细胞系LA-N-5在体外生长受抑制并发生形态分化。现已表明，LA-N-5细胞表达免疫反应性VIP并带有特异性VIP受体。通过竞争性抑制或受体阻断对内源性VIP进行拮抗，可增加细胞增殖，这表明VIP在正常生长调节中起作用。在这些细胞的视黄酸诱导分化过程中，细胞内和细胞外的VIP水平也显著增加。此外，随着细胞分化，VIP受体表达明显增加。这些受体仍然具有功能，这可通过对外源VIP产生的可检测cAMP水平的相应增加得到证明。结论是，VIP是神经母细胞瘤细胞生长和分化的正常自动调节因子，视黄酸介导的分化可能部分归因于内源性VIP。
