Ehlers R A, Kim Sh, Zhang Y, Ethridge R T, Murrilo C, Hellmich M R, Evans D B, Townsend C M, Mark Evers B
Departments of Surgery, The University of Texas Medical Branch, Galveston, Texas 77555-0536, USA.
Ann Surg. 2000 Jun;231(6):838-48. doi: 10.1097/00000658-200006000-00008.
To determine the prevalence of gastrointestinal (GI) peptide receptor expression in pancreatic cancers, and to further assess signaling mechanisms regulating neurotensin (NT)-mediated pancreatic cancer growth.
Pancreatic cancer remains one of the leading causes of GI cancer death; novel strategies for the early detection and treatment of these cancers is required. Previously, the authors have shown that NT, an important GI hormone, stimulates the proliferation of an NT receptor (NTR)-positive pancreatic cancer.
A total of 26 human pancreatic adenocarcinomas, obtained after resection, and 5 pancreatic cancer xenografts were analyzed for expression of NTR, vasoactive intestinal peptide receptor (VIPR), substance P receptor (SPR), and gastrin-releasing peptide receptor (GRPR). In addition, NTR expression, [Ca2+]i mobilization, and growth in response to NT was determined in L3.6, a metastatic pancreatic cancer cell line.
Neurotensin receptor was expressed in 88% of the surgical specimens examined and all five of the pancreatic cancer xenografts. In contrast, VIPR, SPR, and GRPR expression was detected in 31%, 27%, and 8% of pancreatic cancers examined, respectively. Expression of NTR, functionally coupled to the Ca2+ signaling pathway, was identified in L3.6 cells; treatment with NT (10 micromol/L) stimulated proliferation of these cells.
The authors demonstrated NTR expression in most of the pancreatic adenocarcinomas examined. In contrast, VIPR, SPR, and GRPR expression was detected in fewer of the pancreatic cancers. The expression of NTR and other peptide receptors suggests the potential role of endocrine manipulation in the treatment of these cancers. Further, the presence of GI receptors may provide for targeted chemotherapy or radiation therapy or in vivo scintigraphy for early detection.
确定胃肠道（GI）肽受体在胰腺癌中的表达情况，并进一步评估调节神经降压素（NT）介导的胰腺癌生长的信号传导机制。
胰腺癌仍然是胃肠道癌症死亡的主要原因之一；需要新的策略来早期检测和治疗这些癌症。此前，作者已经表明，NT作为一种重要的胃肠道激素，可刺激NT受体（NTR）阳性胰腺癌的增殖。
对26例切除后获得的人胰腺腺癌和5个胰腺癌异种移植瘤进行分析，检测NTR、血管活性肠肽受体（VIPR）、P物质受体（SPR）和胃泌素释放肽受体（GRPR）的表达。此外，在转移性胰腺癌细胞系L3.6中测定NTR表达、[Ca2+]i动员以及对NT的反应性生长情况。
在所检查的手术标本中，88%表达神经降压素受体，所有5个胰腺癌异种移植瘤均表达该受体。相比之下，分别在31%、27%和8%的所检查胰腺癌中检测到VIPR、SPR和GRPR表达。在L3.6细胞中鉴定出与Ca2+信号通路功能偶联的NTR表达；用NT（10微摩尔/升）处理可刺激这些细胞增殖。
作者证明在所检查的大多数胰腺腺癌中存在NTR表达。相比之下，在较少的胰腺癌中检测到VIPR、SPR和GRPR表达。NTR和其他肽受体的表达提示内分泌调节在这些癌症治疗中的潜在作用。此外，胃肠道受体的存在可能为靶向化疗或放疗或体内闪烁显像用于早期检测提供条件。
