Rønnov-Jensen D, Gether U, Fahrenkrug J
Department of Clinical Chemistry, Bispebjerg Hospital, Copenhagen, Denmark.
Eur J Clin Invest. 1991 Apr;21(2):154-60. doi: 10.1111/j.1365-2362.1991.tb01804.x.
To elucidate the biosynthetic processing of the precursor for vasoactive intestinal peptide (prepro-VIP) in tumours producing VIP we have used newly developed radioimmunoassays directed against the five functional domains of the VIP precursor molecule: preproVIP 22-79, peptide histidine methionine (PHM), preproVIP 111-122, VIP and preproVIP 156-170 in combination with HPLC to identify and quantify the peptides in tumour specimen and plasma from patients with the watery diarrhoea syndrome. Elevated quantities of all the five peptides were found in the 13 tumours (nine neurogenic tumours, one pheochromocytoma, three pancreatic carcinomas) examined. The preproVIP derived peptides were expressed in non-equimolar amounts and the relative proportion of the various peptides differed markedly from tumour to tumour. The pheochromocytoma was the only tumour type which contained large amounts of preproVIP 156-170 in comparison with the other peptides. A proportion of the VIP precursor which varied from 7% to 73% followed a pathway in which the dibasic conversion site after PHM was uncleaved as evidenced by the presence of PHV, a C-terminally extended form of PHM. It was also found that unlike normal tissue a fraction of the C-terminal VIP precursor peptide, preproVIP 156-170, was having its C-terminal lysine residue removed during processing. The findings indicate that various post-translational processing pathways of preproVIP exist. All the peptide sequences produced in the tumour tissue were secreted as evidenced by their presence in plasma in elevated concentrations. The plasma levels of preproVIP 22-79, preproVIP 111-122 and PHV exceeded those of the remaining preproVIP-derived peptides suggesting that determination of these peptides in patients with VIP-secreting tumours may be better markers than VIP.
为阐明产生血管活性肠肽（前血管活性肠肽，prepro-VIP）的肿瘤中该前体的生物合成过程，我们使用了新开发的针对VIP前体分子五个功能域的放射免疫分析法：preproVIP 22 - 79、肽组氨酸蛋氨酸（PHM）、preproVIP 111 - 122、VIP和preproVIP 156 - 170，并结合高效液相色谱法（HPLC）来鉴定和定量水样腹泻综合征患者肿瘤标本和血浆中的肽。在所检查的13个肿瘤（9个神经源性肿瘤、1个嗜铬细胞瘤、3个胰腺癌）中发现所有这五种肽的量均升高。preproVIP衍生的肽以非等摩尔量表达，并且各种肽的相对比例在不同肿瘤之间有显著差异。嗜铬细胞瘤是唯一与其他肽相比含有大量preproVIP 156 - 170的肿瘤类型。7%至73%不等比例的VIP前体遵循一种途径，即PHM后的双碱性转换位点未被切割，这可通过PHV（PHM的C末端延伸形式）的存在得到证明。还发现与正常组织不同，一部分C末端VIP前体肽preproVIP 156 - 170在加工过程中其C末端赖氨酸残基被去除。这些发现表明存在preproVIP的各种翻译后加工途径。肿瘤组织中产生的所有肽序列均被分泌，这可通过它们在血浆中以升高的浓度存在得到证明。preproVIP 22 - 79、preproVIP 111 - 122和PHV的血浆水平超过了其余preproVIP衍生肽的水平，这表明在分泌VIP的肿瘤患者中测定这些肽可能比测定VIP是更好的标志物。
