The stroma of healthy pancreases contains various non-hematopoietic, non-endothelial mesenchymal cells. It is altered by chronic inflammation which in turn is a major contributor to the development of pancreatic adenocarcinoma (PDAC). In PDAC, the stroma plays a decisive and well-investigated role for tumor progression and therapy response. This review addresses the central role of stromal cells in the early inflammation-driven development of PDAC. It focuses on major subpopulations of pancreatic mesenchymal cells, i.e., fibroblasts, pancreatic stellate cells, and multipotent stroma cells, particularly their activation and functional alterations upon chronic inflammation including the development of different types of carcinoma-associated fibroblasts. In the second part, the current knowledge on the impact of activated stroma cells on acinar-to-ductal metaplasia and the transition to pancreatic intraepithelial neoplasia is summarized. Finally, putative strategies to target stroma cells and their signaling in early pancreatic carcinogenesis are reflected. In summary, the current data show that the activation of pancreatic stroma cells and the resulting fibrotic changes has pro- and anti-carcinogenetic effects but, overall, creates a carcinogenesis-promoting microenvironment. However, this is a dynamic process and the therapeutic targeting of specific pathways and cells requires in-depth knowledge of the molecular interplay of various cell types.
健康胰腺的基质中含有多种非造血、非内皮来源的间充质细胞。慢性炎症会改变这些细胞的状态，而这种改变正是胰腺导管腺癌发生发展的重要驱动因素。在胰腺导管腺癌中，基质对肿瘤进展和治疗反应起着决定性作用，这一机制已得到充分研究。本综述探讨了基质细胞在炎症驱动的胰腺导管腺癌早期发生过程中的核心作用，重点关注胰腺间充质细胞的主要亚群——即成纤维细胞、胰腺星状细胞和多能基质细胞，特别是它们在慢性炎症状态下的活化与功能改变，包括不同类型癌相关成纤维细胞的形成机制。第二部分总结了当前关于活化基质细胞对腺泡-导管化生及胰腺上皮内瘤变转化影响的研究进展。最后探讨了针对早期胰腺癌发生过程中基质细胞及其信号通路的潜在干预策略。现有数据表明，胰腺基质细胞的活化及其引发的纤维化改变同时具有促癌和抑癌双重效应，但总体而言会形成促进癌发生的微环境。然而这一过程具有动态演变的特性，针对特定通路和细胞的治疗策略需要深入理解多种细胞类型间的分子互作机制。
肿瘤(癌症)患者之家