High-molecular-weight hyaluronan produced by activated pancreatic stellate cells promotes pancreatic cancer cell migration via paracrine signaling
High-molecular-weight hyaluronan produced by activated pancreatic stellate cells promotes pancreatic cancer cell migration via paracrine signaling
复制标题
活化的胰腺星状细胞产生的高分子量透明质酸通过旁分泌信号促进胰腺癌细胞迁移。
DOI：
10.1016/j.bbrc.2019.05.167
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发表时间：
2019-07-30
影响因子：
3.1
通讯作者：
Liang Zhiyong
中科院分区：
文献类型：
--
作者：
Lu Junliang;Wang Lili;Liang Zhiyong
背景资料：多糖透明质酸（HA）在胰腺癌（PC）组织中含量丰富，并在体外促进胰腺癌细胞（PCC）的运动。然而，关于胰腺癌间质中是否存在高分子量HA（HMW-HA）或低分子量HA（LMW-HA）以及PC组织中的PCC或胰腺星状细胞（PSC）是否产生HA存在争议。因此，我们的目的是表征的分子量和来源的HA在PC组织，促进癌细胞motility.Methods：我们分析了透明质酸合成酶2（HAS 2）和水解酶透明质酸酶1（HYAL 1）的PCC线和胰腺星状细胞（PSC）的表达，使用实时PCR。定量和定性检测PCC系和PSC以及PC组织中上清液中HA的产生。最后，我们敲低HYAL 1在PCC系PANC-1细胞中的表达，并分析对细胞migration.Results的影响：HAS 2在活化的PSC（aPSC）中大量表达，但在静止的PSC（qPSC）和PCC系中表达较少。HYAL 1的基线表达在细胞类型之间没有差异。aPSC细胞培养上清中HMW-HA的浓度高于PCC细胞培养上清中HMW-HA的浓度。外源性HMW-HA处理可促进PANC-1细胞运动。结论：aPSC是间质HMW-HA的重要来源，其以HYAL 1依赖的方式促进PCC迁移。(C)2019爱思唯尔公司All rights reserved.
Background: The polysaccharide hyaluronan (HA) is abundant in pancreatic cancer (PC) tissue and promotes pancreatic cancer cell (PCC) motility in vitro. However, it is controversial as to whether high-molecular-weight HA (HMW-HA) or low-molecular weight HA(LMW-HA) is present in the pancreatic cancer stroma and whether PCC or pancreatic stellate cell (PSC) in PC tissue produces HA. We thereby aim to characterize the molecular weight and source of HA in PC tissue that promotes cancer cell motility.Methods: We analyzed the expression of hyaluronan synthase 2 (HAS2) and the hydrolyzing enzyme hyaluronidase 1 (HYAL1) in PCC lines and pancreatic stellate cells (PSCs) using real-time PCR. HA production in the supernatant of PCC lines and PSCs and in PC tissues was quantitatively and qualitatively examined. Finally, we knocked down HYAL1 expression in one of the PCC line PANC-1 cells and analyzed the impact on cell migration.Results: HAS2 was abundantly expressed in activated PSCs (aPSCs) but less so in quiescent PSCs (qPSCs) and PCC lines. The baseline expression of HYAL1 did not differ among the cell types. The concentration of HMW-HA was higher in the supernatant of aPSCs than in that of PCC lines. Treatment with exogenous HMW-HA promoted PANC-1 cell motility. Knockdown of HYAL1 decreased HMW-HA-promoted PANC-1 cell migration, which was accompanied by a decrease in intracellular HA levels.Conclusion: aPSCs are an important source of stromal HMW-HA, which promotes PCC migration in an HYAL1-dependent manner in PC. (C) 2019 Elsevier Inc. All rights reserved.