Desmoplasia of pancreatic ductal adenocarcinoma.
Desmoplasia of pancreatic ductal adenocarcinoma.
复制标题
胰腺导管腺癌的脱木质。
DOI：
10.1016/j.cgh.2009.07.039
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发表时间：
2009-11
期刊：
影响因子：
--
通讯作者：
Gukovskaya A
中科院分区：
文献类型：
--
作者：
Pandol S;Edderkaoui M;Gukovsky I;Lugea A;Gukovskaya A
胰腺导管腺癌（PDAC）是最常见的胰腺癌，其特征是显著的结缔组织增生。结缔组织增生由细胞外基质（ECM）蛋白、肌成纤维胰腺星状细胞和与多种细胞因子、生长因子和ECM代谢酶相关的免疫细胞组成。这种复杂基质过程参与致癌的机制才刚刚开始得到重视。最近的研究表明，星状细胞在ECM蛋白的产生以及促进癌细胞生长的细胞因子和生长因子中的关键作用都存在于PDAC的结缔组织部分。此外，ECM蛋白和促结膜增生分泌生长因子与PDAC癌细胞的相互作用激活细胞内信号，包括活性氧，使癌细胞抵抗死亡。这些发现提示PDAC的结缔组织增生是调节PDAC癌变及对治疗反应的关键因素。更好地了解PDAC机制中结缔组织形成的生物学将可能为更好地治疗这种毁灭性癌症提供重要的机会。
Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and is characterized by remarkable desmoplasia. The desmoplasia is composed of extracellular matrix (ECM) proteins, myofibroblastic pancreatic stellate cells, and immune cells associated with a multitude of cytokines, growth factors, and ECM metabolizing enzymes. The mechanisms of participation of this complex matrix process in carcinogenesis are only starting to be appreciated. Recent studies showed key roles for stellate cells in the production of ECM proteins as well as cytokines and growth factors that promote the growth of the cancer cells all present in the desmoplastic parts of PDAC. In addition, interactions of ECM proteins and desmoplastic secreted growth factors with the cancer cells of PDAC activate intracellular signals including reactive oxygen species that act to make the cancer cells resistant to dying. These findings suggest that the desmoplasia of PDAC is a key factor in regulating carcinogenesis of PDAC as well as responses to therapies. A better understanding of the biology of desmoplasia in the mechanism of PDAC will likely provide significant opportunities for better treatments for this devastating cancer.