Pancreatic stellate cell: Pandora's box for pancreatic disease biology.
Pancreatic stellate cell: Pandora's box for pancreatic disease biology.
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DOI：
10.3748/wjg.v23.i3.382
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发表时间：
2017-01-21
影响因子：
4.3
通讯作者：
Talukdar R
中科院分区：
文献类型：
--
作者：
Bynigeri RR;Jakkampudi A;Jangala R;Subramanyam C;Sasikala M;Rao GV;Reddy DN;Talukdar R
胰腺星状细胞(PSCs)在20世纪80年代初被发现，但在1998年后，随着从小鼠和人来源分离和培养PSCs的方法的发展，PSCs受到了极大的关注。在生理条件下，PSCs只占所有胰腺细胞的一小部分，但对于维持正常的胰腺结构是必不可少的。静止期PSCs的特征是存在富含维生素A的脂滴。当PSC被激活时，这些核周脂滴从胞浆中消失，获得肌成纤维细胞样表型，并表达激活标记α-平滑肌肌动蛋白。在慢性胰腺炎(CP)和胰腺导管腺癌(PDAC)中，PSC通过涉及不同细胞因子的自分泌环路维持其激活的表型，并促进进行性纤维化。一些途径(如JAK-STAT、Smad、Wnt信号、Hedgehog等)、转录因子和miRNAs参与了PSCs的炎症和促纤维化功能。在PDAC中，PSCs的作用远远超出纤维化/结缔组织增生症。现在研究表明，PSCs参与了胰腺癌细胞和癌症间质之间的显著串扰。这些相互作用导致肿瘤进展、转移、肿瘤缺氧、免疫逃避和耐药性。这是针对PSCs和癌症间质的治疗性临床前和临床试验的基本原理。
Pancreatic stellate cells (PSCs) were identified in the early 1980s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin. PSCs maintain their activated phenotype via an autocrine loop involving different cytokines and contribute to progressive fibrosis in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC). Several pathways (e.g., JAK-STAT, Smad, Wnt signaling, Hedgehog etc.), transcription factors and miRNAs have been implicated in the inflammatory and profibrogenic function of PSCs. The role of PSCs goes much beyond fibrosis/desmoplasia in PDAC. It is now shown that PSCs are involved in significant crosstalk between the pancreatic cancer cells and the cancer stroma. These interactions result in tumour progression, metastasis, tumour hypoxia, immune evasion and drug resistance. This is the rationale for therapeutic preclinical and clinical trials that have targeted PSCs and the cancer stroma.