Centers for Cancer Pharmacology and Excellence in Environmental Toxicology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Pancreas. 2011 May;40(4):557-66. doi: 10.1097/MPA.0b013e318214efaf.
Pancreatic stellate cells (PSCs) are important players in pancreatic fibrosis and are major contributors to the extracellular matrix proteins observed with the stromal response characteristic of pancreatic ductal adenocarcinoma (PDAC). Pancreatic stellate cells are also believed to secrete soluble factors that promote tumor progression; however, no comprehensive analysis of the PSC proteome in either the quiescent or the activated state has been reported.
Using 2-dimensional tandem mass spectrometry and the RLT-PSC cell line, we present the first comprehensive study describing and comparing the quiescent and activated human PSC-secreted proteomes.
Very few proteins are secreted in the quiescent state. In stark contrast, activated PSCs secreted a vast array of proteins. Many of these proteins differed from those secreted by PDAC-derived cell lines. Proteins associated with wound healing, proliferation, apoptosis, fibrosis, and invasion were characterized. Selected proteins were verified in human tissue samples from PDAC, dysplastic pancreas, and normal pancreas using Western blot analysis and immunohistochemical staining.
Our study represents the first comprehensive analysis of proteins secreted by PSCs. These findings lay the foundation for characterizing PSC-derived proteins involved in stroma-tumor interactions and the promotion of pancreatitis and PDAC.
胰腺星状细胞（PSCs）是胰腺纤维化的重要参与者，也是胰腺导管腺癌（PDAC）特征性基质反应中观察到的细胞外基质蛋白的主要贡献者。胰腺星状细胞也被认为分泌促进肿瘤进展的可溶性因子；然而，尚未报道静止或激活状态下的胰腺星状细胞蛋白质组的全面分析。
使用二维串联质谱和 RLT-PSC 细胞系，我们首次全面描述和比较了静止和激活的人胰腺星状细胞分泌的蛋白质组。
静止状态下很少有蛋白质被分泌。相比之下，激活的胰腺星状细胞分泌了大量的蛋白质。这些蛋白质中有许多与 PDAC 衍生的细胞系分泌的蛋白质不同。鉴定出与伤口愈合、增殖、凋亡、纤维化和侵袭相关的蛋白质。使用 Western blot 分析和免疫组织化学染色，在来自 PDAC、发育不良胰腺和正常胰腺的人类组织样本中验证了选定的蛋白质。
我们的研究代表了对胰腺星状细胞分泌的蛋白质进行的首次全面分析。这些发现为表征参与基质-肿瘤相互作用以及促进胰腺炎和 PDAC 的胰腺星状细胞衍生蛋白奠定了基础。
