Pence J C, Shorter N A
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710.
Cancer Res. 1990 Aug 15;50(16):5177-83.
Neuroblastoma, a tumor of the sympathetic nervous system, is the most common solid malignancy of childhood outside the central nervous system. Vasoactive intestinal peptide (VIP) is produced by some of these tumors, and elevated serum levels correlate with tumor cell differentiation and a favorable prognosis. It has previously been demonstrated that human neuroblastoma cell lines LA-N-5 and IMR-32 will differentiate in vitro when exposed to retinoic acid. It is now shown that VIP also induces in vitro differentiation of these neuroblastoma lines. LA-N-5 or IMR-32 cells were grown in the presence of different concentrations of VIP. Cell proliferation was suppressed, as measured by cell count, incorporation of [3H]thymidine, and measurement of the proliferation index. The degree of suppression correlated with the concentration of VIP, and the effect was indistinguishable, on a molar basis, from that seen when cells were treated with retinoic acid. Similarly, the morphological changes seen in the VIP-treated cells were the same as those seen in retinoic acid-treated ones. The effects of VIP on both cell lines, like those of retinoic acid, are reversible. The human neuroepithelioma line CHP-100, is much less sensitive to either agent. Vasoactive intestinal peptide is the first substance shown to cause differentiation of neuroblastoma cells in vitro which is also known clinically to have a specific association with that tumor. It is postulated that VIP may play a key role in the well-documented maturation of these tumors in vivo and in the normal development of the sympathetic nervous system. These findings may also have therapeutic implications for the management of this frustrating childhood malignancy.
神经母细胞瘤是一种交感神经系统肿瘤，是中枢神经系统以外儿童期最常见的实体恶性肿瘤。一些此类肿瘤会产生血管活性肠肽（VIP），血清水平升高与肿瘤细胞分化及良好预后相关。此前已证明，人神经母细胞瘤细胞系LA-N-5和IMR-32在暴露于视黄酸时会在体外分化。现在发现VIP也能诱导这些神经母细胞瘤系在体外分化。将LA-N-5或IMR-32细胞在不同浓度的VIP存在下培养。通过细胞计数、[3H]胸苷掺入及增殖指数测量发现细胞增殖受到抑制。抑制程度与VIP浓度相关，且从摩尔基础来看，其效果与用视黄酸处理细胞时所见效果无法区分。同样，经VIP处理的细胞中观察到的形态变化与经视黄酸处理的细胞中所见相同。VIP对这两种细胞系的作用，与视黄酸一样，是可逆的。人神经上皮瘤细胞系CHP-100对这两种药物的敏感性要低得多。血管活性肠肽是第一种被证明能在体外引起神经母细胞瘤细胞分化的物质，临床上也已知其与该肿瘤有特定关联。据推测，VIP可能在这些肿瘤在体内充分记录的成熟过程以及交感神经系统的正常发育中起关键作用。这些发现也可能对这种令人沮丧的儿童恶性肿瘤的治疗具有启示意义。
