Department of Surgery, Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, Galveston, Texas 77555-0722, USA.
Curr Opin Endocrinol Diabetes Obes. 2010 Feb;17(1):33-9. doi: 10.1097/MED.0b013e328333faf8.
Chronic infection of the gastric mucosa with Helicobacter pylori has long been recognized as a significant risk factor for gastric cancer, and indeed, this model represents the prototypical inflammation-associated cancer. In this review, we present the latest clinical and experimental evidence showing that gastrin peptides and their receptors [the cholecystokinin (CCK2) receptors] potentiate the progression of gastric cancer and other gastrointestinal malignancies in the presence of inflammation.
We highlight the feed-forward mechanisms by which gastrin and CCK2 receptor expression are upregulated during inflammation and in gastrointestinal cancers, summarize gastrin's proinflammatory role by inducing the production of cyclooxgenase-2 (COX-2) and interleukin-8 (IL-8), and relate evidence suggesting that gastrin and their receptors modulate the function of immune cells and fibroblasts following cellular stress, injury, repair, as well as during cancer progression.
We discuss trends for future studies directed toward the elucidation of gastrin peptides' role in regulating intercellular molecular signaling mechanisms between local and circulating immune cells, fibroblasts, epithelial cells, and other cell types in the microenvironments of inflammation-related cancers. Elucidation of the molecular and cellular pathways that relate inflammation with cancer may provide additional opportunities to develop complementary therapies that target the inflammatory microenvironment of the cancer.
长期以来，幽门螺杆菌（H. pylori）慢性感染被认为是胃癌的一个重要危险因素，事实上，这种模型代表了典型的炎症相关癌症。在这篇综述中，我们提出了最新的临床和实验证据，表明在炎症存在的情况下，胃泌素肽及其受体（胆囊收缩素（CCK2）受体）增强了胃癌和其他胃肠道恶性肿瘤的进展。
我们强调了在炎症和胃肠道癌症中胃泌素和 CCK2 受体表达上调的正反馈机制，总结了胃泌素通过诱导环氧化酶-2（COX-2）和白细胞介素-8（IL-8）的产生而发挥促炎作用，并提出了证据表明胃泌素及其受体在细胞应激、损伤、修复以及癌症进展过程中调节免疫细胞和成纤维细胞的功能。
我们讨论了未来研究的趋势，旨在阐明胃泌素肽在调节炎症相关癌症微环境中局部和循环免疫细胞、成纤维细胞、上皮细胞和其他细胞类型之间细胞间分子信号机制中的作用。阐明将炎症与癌症联系起来的分子和细胞途径可能为开发靶向癌症炎症微环境的补充疗法提供更多机会。
