胶原蛋白在胰腺癌中的研究进展

Research Progress of Collagen in Pancreatic Cancer

胶原蛋白(collagen)是一个广泛分布于全身的三螺旋蛋白大家族,是由三条α肽链构成的三聚螺旋体结构。可以根据它们的共同结构域、同源性和功能分为七类,分别是:纤维性胶原、网状胶原蛋白、FACITs (fibril-associated collagens with interrupted triple helices)、MACITs (三螺旋中断的膜相关胶原)、锚定纤维、珠丝形成胶原蛋白、MULTIPLEXIN (多个三螺旋结构域和中断)/产生内皮抑素的胶原蛋白。近年来有关研究发现,胶原蛋白由促结缔组织基质内的胰腺星状细胞(Pancreatic stellate cells, PSC)产生并促进胰腺癌(pancreatic cancer, PC)细胞粘附、增殖、迁移和化学抗性。但也有大量研究发现有高基质含量的患者生存率反而更高;去除癌相关成纤维细胞(Cancer-associated fibroblasts, CAFs)基因的患癌小鼠生存率更低;I型胶原蛋白的缺失会加速胰腺癌的进展。以上研究证实了,胰腺癌的间质成分可能通过复杂的机制影响着胰腺癌的发生发展。并且与胰腺癌的发生发展密切相关。本文简要总结与胰腺癌相关的胶原蛋白以及它们之间的关系,包括IV型、VI型、X型胶原蛋白,并有望成为胰腺癌的肿瘤标志物以及为胰腺癌的诊断及治疗提供初步的理论依据。

Collagen is a large family of triple helix proteins widely distributed throughout the body, and is a triple helix structure composed of three α-peptide chains. It can be divided into seven categories according to their common domains, homology and function, namely: fibrillar collagens, reticular collagens, FACITs (fibril-associated collagens with interrupted triple helices), MACITs (membrane-associated triple helices interrupted collagen), anchoring fibers, bead-forming collagen, MULTIPLEXIN (multiple triple helical domains and interruptions)/endostatin-producing collagen. Recent studies have found that collagen is produced by pancreatic stellate cells (PSC) in the connective tissue matrix and promotes cell adhesion, proliferation, migration and chemoresistance in pancreatic cancer (PC). However, a large number of studies have also found that patients with high stromal content have a higher survival rate;the survival rate of mice of cancer-associated fibroblasts (CAFs) gene deletion is lower;the loss of type I collagen will accelerate pancreatic cancer progression. The above studies have confirmed that the interstitial components of pancreatic cancer may affect the occurrence and development of pancreatic cancer through complex mechanisms. And it is closely related to the occurrence and development of pancreatic cancer. This article briefly summarizes the collagens related to pancreatic cancer and the relationship between them, including type IV, type VI, and type X collagen, which are expected to become tumor markers of pancreatic cancer and provide a preliminary theory for the diagnosis and treatment of pancreatic cancer.