Department of Surgery, Clinical Sciences Lund, Lund University and Lund University Hospital, Lund, Sweden.
Pancreatology. 2010;10(6):673-81. doi: 10.1159/000320711. Epub 2011 Jan 18.
Pancreatic ductal adenocarcinoma is an aggressive and highly lethal disease frequently characterized by a dense stromal or desmoplastic response. Accumulating evidence exists that tumor desmoplasia plays a central role in disease progression and that e.g. activated pancreatic stellate cells (PSCs) are responsible for the excess matrix production. The mechanisms underlying the tumor versus stroma interplay are complex. Pancreatic cancer cells release mitogenic and fibrogenic stimulants, such as transforming growth factor β(1), platelet-derived growth factor (PDGF), sonic hedgehog, galectin 3, endothelin 1 and serine protease inhibitor nexin 2, all of which may promote the activated PSC phenotype. Stellate cells in turn secrete various factors, including PDGF, stromal-derived factor 1, epidermal growth factor, insulin-like growth factor 1, fibroblast growth factor, secreted protein acidic and rich in cysteine, matrix metalloproteinases, small leucine-rich proteoglycans, periostin and collagen type I that mediate effects on tumor growth, invasion, metastasis and resistance to chemotherapy. This review intends to shed light on the mechanisms by which PSCs in the stroma influence pancreatic cancer development. The increased understanding of this interaction will be of potential value in designing new modalities of targeted therapy. and IAP.
胰腺导管腺癌是一种侵袭性和高度致命的疾病，常以致密的基质或纤维化为特征。越来越多的证据表明，肿瘤间质在疾病进展中起着核心作用，例如激活的胰腺星状细胞（PSCs）负责过量的基质产生。肿瘤与基质相互作用的机制很复杂。胰腺癌细胞释放有丝分裂原和纤维生成刺激物，如转化生长因子β(1)、血小板衍生生长因子（PDGF）、刺猬信号通路、半乳糖凝集素 3、内皮素 1 和丝氨酸蛋白酶抑制剂神经氨酸酶 2，所有这些都可能促进激活的 PSC 表型。星状细胞反过来分泌各种因子，包括 PDGF、基质衍生因子 1、表皮生长因子、胰岛素样生长因子 1、成纤维细胞生长因子、富含半胱氨酸的酸性分泌蛋白、基质金属蛋白酶、小富含亮氨酸的蛋白聚糖、骨膜蛋白和 I 型胶原，这些因子介导对肿瘤生长、侵袭、转移和化疗耐药的影响。这篇综述旨在阐明基质中的 PSCs 影响胰腺癌细胞发展的机制。增加对这种相互作用的理解将有助于设计新的靶向治疗模式。和 IAP。
