人胰腺癌高肝转移细胞株的建立及其意义

背景与目的：胰腺癌肝转移是胰腺癌晚期常见的症状，也是主要的致死原因。肿瘤转移是一个相当复杂的过程，建立胰腺癌肝转移模型是研究胰腺癌肝转移机理关键的一步。本研究通过连续人胰腺癌SW1990细胞脾脏移植法筛选出高肝转移胰腺癌细胞株，并对其转移相关特性进行分析。方法：人胰腺癌SW1990细胞脾内注射出现肝转移病灶后，将肝转移病灶肿瘤细胞体外原代培养扩增，再脾内注射出现肝转移病灶，此过程重复4次筛选到SW1990H4；然后比较SW1990H4和SW1990细胞株的核型、细胞体外增殖、细胞周期、体外侵袭、体内成瘤性、转移性和部分转移相关基因MMP-2、MMP-9、VEGF、bFGF和E—cadherin mRNA表达水平的差异。结果：SW1990H4和SW1990细胞株的核型及周期差异无显著性（P〉0．05）；SW1990H4体外细胞增殖速度、体外侵袭能力、移植瘤增长速度和肝转移率均显著高于SW1990细胞株（P〈0．05），SW1990H4细胞MMP-2、VEGF、bFGF和E—cadherin mRNA表达水平均高于SW1990，只有MMP-9 mRNA表达水平低于SW1990。结论：SW1990H4是人胰腺癌高肝转移细胞株，可应用于胰腺癌肝转移机制研究和抗肝转移药物的筛选。     

胰腺癌组织和细胞的耐药性与ABC转运蛋白基因1 的关系

[摘要] 目的：探讨胰腺癌耐药性与ABC转运蛋白基因1（ABCB1）的表达及其启动子甲基化的关系。方法：选用2015 年8月至2018 年8 月福建省肿瘤医院病理确诊的15 例胰腺癌及癌旁组织、3 例正常胰腺组织标本以及胰腺癌细胞株SW1990,用间歇浓度梯度倍增法将SW1990 细胞株诱导分化为吉西他滨（GEM）耐药胰腺癌细胞株SW1990/GZ。用qPCR分别检测胰腺癌及癌旁组织和SW1990、SW1990/GZ细胞中ABCB1 表达水平,用MSP-PCR法检测胰腺癌组织和SW1990、SW1990/GZ细胞中ABCB1启动子区域甲基化程度。结果：与SW1990 相比,SW1990/GZ细胞空泡增多、核分裂像增加、呈现团块生长,并呈现更强的耐药性（P<0.05）。胰腺癌组织中ABCB1 表达水平明显高于癌旁组织（P<0.01）。SW1990 和SW1990/GZ细胞中ABCB1 表达水平显著高于正常胰腺组织（P<0.05 或P<0.01）,其中SW1990/GZ 细胞中ABCB1 表达水平高于SW1990 细胞（P<0.05）。SW1990 和SW1990/GZ细胞及正常胰腺组织中的ABCB1 启动子均呈低甲基化状态。胰腺癌和正常胰腺组织中甲基化率分别为6.7%（1/15）及0.00%（0/3）,差异无统计学意义（均P>0.05）。结论：胰腺癌组织和细胞中ABCB1 表达增高与耐药性有关,但其基因表达不依赖于启动子的甲基化调控。     

siRNA沉默S100P基因对胰腺癌细胞的生长抑制作用

[目的]探讨小干扰RNA（siRNA）沉默S100P基因后对胰腺癌SW1990细胞株生长的影响。[方法]化学合成针对S100P基因的siRNA,用脂质体转染试剂将siRNA体外转染至人胰腺癌SW1990细胞中,48h后收集细胞,分别提取细胞总RNA和蛋白。用实时定量RT-PCR测定S100P基因mRNA水平的表达;免疫印迹测定S100P蛋白的表达;MTT法测定细胞的生长曲线。[结果]转染siRNA后,S100P基因在mRNA水平上表达减少了77%,蛋白表达降低了74%,均显著性低于对照组。siRNA-S100P明显抑制细胞生长。[结论]应用RNAi技术沉默S100P基因可以降低人胰腺癌SW1990细胞株中S100P表达,抑制细胞生长。     

MYEOV对人胰腺癌细胞增殖和迁移的影响

目的 探讨骨髓瘤过表达基因MYEOV在人胰腺癌细胞中的表达情况及其下调对胰腺癌SW1990细胞增殖和迁移能力的影响。方法 构建慢病毒载体GV248，转染胰腺癌细胞株SW1990获得SW1990-sh1和SW1990-sh2两个实验组，以空白质粒转染作为阴性对照组，未干预细胞为空白对照组。qPCR和Western blot检测转染前后MYEOV mRNA与蛋白的表达水平；CCK-8法测定细胞增殖能力；划痕实验分析细胞迁移能力。qPCR检测TGF-β/SMAD通路中相关SMADs mRNA表达水平。结果 与正常胰腺导管上皮细胞系HPDE6相比，MYEOV mRNA在6株胰腺癌细胞中表达水平明显增加（P<0.01）；但仅在PANC-1和SW1990细胞系中检测到低水平MYEOV蛋白表达。实验组中MYEOV mRNA和蛋白表达均明显下调。与对照组相比，SW1990细胞的增殖和迁移能力明显下降（P<0.001）。下调MYEOV能降低TGF-β通路中SMAD1、SMAD4、SMAD5和SMAD9 mRNA表达（P<0.01），而SMAD2、SMAD3和SMAD7 mRNA仅在SW1990-sh2组中表达下调（P<0.01）。结论 MYEOV在胰腺癌细胞系中转录水平高，MYEOV可通过TGF-β/SMAD通路促进胰腺癌细胞的增殖和迁移能力。     

长链非编码RNA MIR31HG在胰腺癌中的表达及其对胰腺癌细胞耐药性的影响

目的分析长链非编码RNA MIR31HG在胰腺癌中的表达情况及其与患者临床特征的关系,探讨其对胰腺癌细胞耐药性的影响。方法采用实时荧光定量逆转录-聚合酶链反应(qRT-PCR)法检测MIR31HG的表达情况,分析MIR31HG表达与胰腺癌患者临床特征的关系。将SiMIR31HG转染至AsPC-1、PANC-1、Capan-2胰腺癌细胞中,分别作为SiA组、SiB组、SiC组;将空载体转染至AsPC-1、PANC-1、Capan-2胰腺癌细胞中,分别作为NC1组、NC2组、NC3组。采用CCK-8实验和Transwell小室检测胰腺癌细胞的增殖和迁移能力。分析下调MIR31HG表达对PANC-1、AsPC-1细胞5-氟尿嘧啶(5-FU)半数抑制浓度(IC50)的影响。检测同一浓度5-FU处理下各组细胞的存活情况。结果胰腺癌组织中MIR31HG的表达水平明显高于癌旁正常组织(P﹤0.01)。胰腺癌细胞AsPC-1、PANC-1、Capan-1、Capan-2、SW1990中MIR31HG的表达水平均高于正常胰腺导管上皮细胞HPDE6c-7(P﹤0.05)。肿瘤直径﹥3 cm、有远处转移、临床分期为Ⅲ～Ⅳ期、分化程度为低分化、CA19-9水平高的胰腺癌患者胰腺癌组织中MIR31HG的表达水平均高于肿瘤直径≤3 cm、无远处转移、临床分期为Ⅰ～Ⅱ期、分化程度为高分化、CA19-9水平低的胰腺癌患者(P﹤0.05)。下调MIR31HG表达后,胰腺癌细胞的迁移和增殖能力均下降(P﹤0.01)。SiA组和SiB组细胞的IC50均低于NC1组和NC2组(P﹤0.05);在同一浓度5-FU处理下,SiA组、SiB组细胞的存活率均低于NC1组和NC2组(P﹤0.05)。结论长链非编码RNA MIR31HG在胰腺癌组织和细胞中的表达水平均较高,且MIR31HG的表达情况可能与胰腺癌患者的肿瘤直径、临床分期、远处转移情况、分化程度、CA19-9水平有关。下调MIR31HG的表达可抑制胰腺癌细胞的增殖和迁移,并可增强胰腺癌细胞对化疗药物的敏感性,降低其耐药性。     

NDRG1下调对吉西他滨干预人胰腺癌细胞 PANC －1增殖及凋亡的影响

目的：观察 siNDRG1干扰对吉西他滨干预的胰腺癌细胞增殖、细胞周期及凋亡的影响并探讨其机制。方法：以 Western blot 法对 PANC －1、BXPC －3、CAPAN －2、SW1990细胞中 NDRG1的表达进行检测;构建靶向 NDRG1的干扰质粒 siNDRG1,转染 PANC －1细胞,以 Western blot 法及（qRT）－PCR 法检测 NDRG1干扰效率;对 siRNA 干扰细胞给予吉西他滨干预,采用 MTT 法检测细胞增殖,PI 法检测细胞周期,流式细胞术检测细胞调亡。结果：Western blot 显示,NDRG1在四组细胞株中均有表达,低分化细胞（PANC －1）中表达量较中分化（BXPC －3）及高分化细胞株（CAPAN －2、SW1990）中高（P ＜0．05）;MTT 显示,吉西他滨干预后 PANC －1细胞在 siNDRG1转染组细胞生长抑制率高于 siNC 组,差异有显著性（P ＜0．01）。PI 法显示,转
　　染 siNDRG1的 PANC －1细胞停留在 G1期比例减少,G2及 S 期比例升高,与 siNC 组对比,差异具有显著性（t＝4．21,P ＜0．05;t ＝3．54,P ＜0．05;t ＝3．29,P ＜0．05）。经吉西他滨处理后,siNDRG1较 siNC 组 G1期及 G2期细胞比例明显减少,S 期细胞比例升高,差异具有显著性（t ＝14．65,P ＜0．01;t ＝13．28,P ＜0．01;t ＝15．17, P ＜0．01）。流式细胞仪检测经吉西他滨处理后 siNDRG1组凋亡率高于 siNC 组,差异有显著性（t ＝22．42,P＜0．001）。结论：对胰腺癌细胞 NDRG1表达进行下调可以增强吉西他滨化疗敏感性,抑制细胞增殖,促进凋亡,可作为胰腺癌治疗新的靶向候选基因。     

STAT3基因沉默对胰腺癌细胞放射敏感性的影响及其机制

目的:探讨信号转导和转录激活因子3（STAT3）基因沉默对人胰腺癌细胞AsPC-1和PANC-1放射敏感性的影响及其机制。方法:体外培养人胰腺癌细胞AsPC-1和PANC-1，通过脂质体转染STAT3 shRNA作为实验组（shSTAT3组），设置阴性对照（shNC组）和空白对照组（NC组）。采用qRT-PCR检测转染后各组AsPC-1和PANC-1细胞中STAT3 mRNA表达水平，Western blot检测细胞中STAT3蛋白表达水平。MTT实验检测各组细胞增殖能力，流式细胞仪检测各组细胞电子射线照射后的凋亡情况，qRT-PCR和Western blot分别检测各组细胞电子射线照射后的Bax、Bcl-2和Caspase-3 mRNA和蛋白的表达情况。结果:shSTAT3组AsPC-1和PANC-1细胞中STAT3 mRNA和蛋白表达水平比NC组和shNC组明显降低（P<0.05）。接受电子射线照射后，shSTAT3组AsPC-1和PANC-1细胞增殖率显著低于shNC组（P<0.05），其细胞凋亡率较shNC组明显升高（P<0.05）。接受电子射线照射后，转染STAT3 shRNA后能够明显上调细胞中Bax和Caspase-3的表达和下调Bcl-2的表达（P<0.05）。结论:沉默STAT3基因能够通过上调Bax和Caspase-3的表达和下调Bcl-2的表达促进细胞凋亡，增强胰腺癌细胞的放射敏感性。     

阻断STAT3信号转导通路对人胰腺癌细胞生长的影响

目的：探讨Janus激酶（Janus kinase，JAK）特异性抑制剂AG490阻断STAT3信号转导通路对高表达STAT3的人胰腺癌细胞系SW1990生长增殖的怍用及其机制。方法：使用AG490处理人胰腺癌细胞系SW1990，MTT法检测细胞增殖状态，流式细胞仪检测细胞凋亡，Western blot检测STAT3信号转导通路成员的表达。结果：AG490作用于人胰腺癌细胞系SW1990后，细胞增殖水平明显下降（P〈0．05）；细胞凋亡百分比显著升高（P〈0．05）；Western blot显示SW1990细胞中磷酸化STAT3（p-STAT3）、bcl-xL和cyclin D1蛋白表达明显降低（P〈0．05）。结论：STAT3信号转导通路在胰腺癌进展过程中起着重要作用；阻断STAT3信号转导通路可抑制人胰腺癌细胞增殖，促进其凋亡；以STAT3信号转导通路为靶点的治疗策略可能为胰腺癌治疗提供新的思路。     

CLDN6对胰腺癌细胞增殖的影响及其在胰腺癌组织中的表达和临床意义研究

目的分析紧密连接蛋白6 (claudin 6,CLDN6)在人胰腺癌组织中的表达及与临床因素间的关系,探究其对人胰腺癌细胞增殖的影响。方法免疫组织化学法及qRT-PCR法检测50例胰腺癌及对应癌旁组织中CLDN6表达,分析其与临床病理因素及预后间的相关性;qRT-PCR法检测胰腺癌不同细胞株（AsPC-1、BxPC-3、Capan-1、PANC-1、HPAC、Hs 766T、MIA Paca-2）与正常胰腺导管上皮细胞株HPDE中CLDN6表达。胰腺癌细胞株脂质体转染CLDN6 siRNA沉默基因,qRT-PCR检测转染情况;MTT法、平板克隆实验检测细各胞增殖能力及克隆形成能力;Western blot检测E-cadherin、N-cadherin、波形纤维蛋白（Vimentin,VIM）及纤维连接蛋白（Fibronectin,FN）表达。结果胰腺癌组织中CLDN6表达水平明显高于癌旁正常组织,差异显著（PP>0.05）,而与TNM分期、肿瘤分化程度及淋巴结转移有关（PVS 18.402月）（PPP结论CLDN6在胰腺癌中高表达,且与患者临床特征及预后相关,其可促进人胰腺癌细胞增殖及克隆形成,机制可能与促进上皮细胞-间充质转化（Epithelial to mesenchymal transformation,EMT）有关。     

羟基喜树碱耐药结肠癌细胞株SW1116/HCPT肿瘤耐药相关基因的表达

目的：分析结肠癌耐药株SW1116／HCPT（羟基喜树碱）肿瘤耐药相关基因的表达情况。方法：对本所新近构建的结肠癌耐药株SW1116／HCPT的肿瘤药物耐受功能分类基因芯片的检测结果进行验证；以实时荧光定量-PCR法检测基因芯片中部分表达有改变的基因；以western blot法分析SW1116／HCPT耐药细胞株与原代细胞株间在p21和MRP2蛋白表达水平上的变化。结果：p21^WAF1/CIP1、MRP2（ABCC2）、BRCA2、CYP3A5等部分表达有改变基因的实时荧光定量-PCR鉴定结果与基因芯片结果基本一致；Western blot检测的p21^WAF1/CIP1和MRP2（ABCC2）蛋白表达水平与其转录水平表达相吻合。结论：基因芯片技术是一种大规模检测多种基因表达的有效方法，新建的结肠癌细胞耐药模型SW1116／HCPT中存在多类肿瘤耐药相关基因在转录水平和翻译水平的表达差异。     

雷公藤内酯醇调节5-脂氧合酶对胰腺癌细胞增殖的影响

目的:探讨雷公藤内酯醇(Triptolide,TL)在胰腺癌细胞中5-脂氧合酶(5-LOX)蛋白的表达及对癌细胞生长的影响.方法:应用免疫细胞化学法检测胰腺癌细胞株SW1990和Capan2中5-LOX蛋白的表达,同时检测TL对胰腺癌细胞株SW1990 5-LOX蛋白表达的影响,采用MTT法和流式细胞术分别检测胰腺癌细胞SW1990的增殖和凋亡.结果:胰腺癌细胞株SW1990和Capan2中均表达5-LOX,并与细胞分化程度有关;TL抑制SW1990中5-LOX蛋白的表达,并抑制胰腺癌细胞SW1990增殖和促进细胞的凋亡,作用随浓度的增加而增强(P＜0.01);细胞的增殖和凋亡与5-LOX蛋白的表达相关(P＜0.01).结论:TL抑制胰腺癌细胞SW1990中5-LOX的表达,并抑制胰腺癌细胞增殖和诱导凋亡,5-LOX代谢途径在胰腺癌细胞的生长中发挥重要作用.     

siRNA沉默caveolin-1基因对胰腺癌细胞迁徙和侵袭影响及其机制的探讨

目的：探讨caveolin-1对胰腺癌细胞PANCl在体外迁徙和侵袭的影响并初步探讨其机制。方法：用siRNA技术抑制胰腺癌PANCl细胞中caveolin-1的表达,构建细胞株PANCl／siRNA作为实验组,空载体细胞株PANCl／shuffle作为对照组。蛋白质印迹法检测细胞内caveolin-1和MMP_7的表达。流式细胞仪分析细胞失巢凋亡指数,黏附实验检测细胞黏附定植的能力,侵袭小室实验检测细胞迁徙和侵袭的能力。结果：PANCl／siRNA细胞的caveolin-1表达被抑制,表达量低于PANC1／shuffle和PANC1细胞株（P〈0．01）;PANCl／siRNA细胞的抗失巢凋亡的能力强于PANcl／shuffle细胞,凋亡指数分别为（（9．24±1．61）％US（17．32±1．79）％,P〈0．01）,PANC1／siRNA的黏附能力强于PANC1／shuffle（0．867±0．153VS0．523±0．072,P〈0．01）;PANC1／siRNA迁入膜内的细胞数多于PANC1／shuffle（142．6±24．35US106．5±10．81,P〈0．05）,PANC1／siRNA细胞侵袭破坏基质胶进入膜内的能力强于PANCl／shuffle（88．9±8．07 S61．3±7．23,P〈0．01）;PANCl／siRNA中MMP-7表达量明显高于PANCl／shuffle（P〈0．01）。结论：caveolin-1通过对MMP-7的调控抑制PANC1细胞的体外迁徙和侵袭。     

microRNA-122抑制胰腺癌细胞增殖、迁移和侵袭

目的 明确microRNA-122(miR-122)在胰腺癌中的表达及miR-122对胰腺癌细胞增殖、迁移和侵袭的作用.方法 采用RT-qPCR方法检测20例胰腺癌组织、胰腺癌细胞株(ASPC1、PANC1、MP和SW1990)和人源正常胰腺导管上皮细胞株(HPDE)中miR-122的表达量.将miR-122模拟类似物...     

In vitro and in vivo evidence that a combination of lapatinib plus S‐1 is a promising treatment for pancreatic cancer

Lapatinib is a small molecule inhibitor of both HER2 and the epidermal growth factor receptor (EGFR). We investigated the effect of treatment with lapatinib alone or in combination with a fluoropyrimidine derivative S‐1 against pancreatic cancer. The HER2/EGFR expression in each of the four pancreatic cancer cell lines MiaPaca‐2, PANC‐1, Capan‐1 and Capan‐2 was measured by flow cytometry. The anti‐tumor effects of lapatinib (30 mg/kg) and/or S‐1 (10 mg/kg) were evaluated using female BALB/c nude mice xenografts generated using these four cell lines. Synergy between lapatinib and S‐1 was examined by median effect analysis in vitro. Resected pancreatic cancer tissues from 137 patients were immunohistochemically stained with anti‐human HER2 and EGFR antibodies. The administration of lapatinib as a single agent substantially suppressed tumor growth in vivo of all pancreatic cancer cell lines examined. A strong correlation was observed between HER2 expression and the anti‐tumor effect of lapatinib in vivo. Lapatinib synergized with S‐1 to inhibit the tumor growth of MiaPaca‐2 and PANC‐1 xenografts. When used as a single agent in vitro, lapatinib barely inhibit the cell growth of any cell line. However, lapatinib synergized with the anti‐tumor activity of the S‐1 components 5‐fluorouracil and 5‐chloro‐2,4‐dihydrogenase against all cell lines. Immunohistochemical staining demonstrated that 70% of the pancreatic cancers overexpressed HER2 and/or EGFR. Both lapatinib monotherapy and combined treatment with S‐1 may be promising treatments for patients with pancreatic cancers; the majority these cancers express lapatinib target molecules. (Cancer Sci 2009; 00: 000–000)     

Expression and promoter methylation analysis of ATP-binding cassette genes in pancreatic cancer

We investigated the relationship of ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP expression and promoter methylation with pancreatic cancer tumorigenesis and drug resistance. Gemcitabine-resistant pancreatic cancer cells, SW1990/GZ (33.3-fold increased resistance), were obtained by treating SW1990 cells with gemcitabine. The expression of ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP was determined by quantitative real-time RT-PCR in the cell lines, 3 normal pancreatic tissues, 15 human pancreatic cancer samples and 15 adjacent tissues. Promoter methylation was determined in cell lines by bisulfite genomic sequencing. ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP were upregulated in SW1990 and SW1990/GZ compared with normal pancreatic tissue, and expression in SW1990/GZ was significantly higher than in SW1990 cells. ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP were upregulated in pancreatic cancer tissues, compared to adjacent tissues. The ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP promoter were hypomethylated in all the cell lines. ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP expression correlated with pancreatic cancer tumorigenesis and drug resistance in a mechanism that is independent of promoter methylation.     

Lipid-dependent proliferation of pancreatic cancer cell lines

Capan 1, a human pancreatic cancer cell line, is routinely grown in 10% fetal calf serum (FCS). In order to characterize the factors needed for its proliferation, FCS was replaced by a synthetic serum (Ultroser G). For Capan 1 proliferation we found that Ultroser G was as efficient as FCS. A subfraction of Ultroser G containing insulin, transferrin, and lipids was found to be responsible for that response since a combination of these compounds reproduced the growth observed with 10% FCS. Lipids stimulated cell proliferation even in the absence of other factors. Other human (MIA PaCa 2, AsPC1, Panc 1) or rat (AR4-2J) pancreatic cancer cell lines tested proliferated in the reconstituted medium containing insulin (100 ng/ml), transferrin (100 micrograms/ml), fatty acid-free albumin (1 mg/ml), and bovine serum lipids (0.7%), as in 10% FCS. Furthermore, the growth of nonpancreatic cell lines (HT29, A431, CREF) was not enhanced by lipids. Lipoproteins were found to be involved in the mitogenic response of pancreatic cells to lipids, whereas phosphatidylcholine and fatty acids were either inefficient or inhibitors (MIA PaCa2 and AR4-2J). Alkaline phosphatase and amylase content, differentiation markers for Capan 1 and AR4-2J cells, respectively, were not modified by the reconstituted medium. These data suggest that lipids, insulin, and transferrin are the essential factors for the proliferation of pancreatic cancer cell lines, reproducing the growth effect of 10% FCS. Moreover, in the absence of most of the seric growth factors, pancreatic cells remained differentiated.     

Tumor-associated MUC5AC stimulates in vivo tumorigenicity of human pancreatic cancer

MUC5AC, a high molecular weight glycoprotein, is overexpressed in the ductal region of human pancreatic cancer but is not detectable in the normal pancreas, suggesting its association with disease development. In the present study, we investigated the in vitro and in vivo effects of MUC5AC knockdown by short interfering RNA (siRNA) in the MUC5AC-overexpressing SW1990 and BxPC3 human pancreatic cancer cell lines in order to clarify its function. Significant decreases in the expression levels of MUC5AC mRNA and protein were observed in SW1990 and BxPC3 cells that had been stably transfected with a MUC5AC siRNA expression vector (SW1990/si-MUC5AC and BxPC3/si-MUC5AC cells) compared to those in cells transfected with an si-mock vector (SW1990/si-mock and BxPC3/si-mock cells). In in vitro studies, neither type of MUC5AC-knockdown cell showed any difference in cell survival, proliferation, or morphology from the si-mock cells or parental cells. However, in vivo xenograft studies demonstrated that MUC5AC knockdown significantly reduced the tumorigenicity and suppressed the tumor growth of si-MUC5AC cells compared to those of the si-mock cells. Immunohistochemical analysis revealed that CD45R/B220+ and Gr-1+ cells had infiltrated into the tumor tissue of the SW1990/si-MUC5AC cells. Furthermore, cancer-associated antigen specific antibodies were detected at high levels in the sera from the SW1990/si-MUC5AC cell-bearing mice. These results suggest that tumor-associated MUC5AC expressed on the surface of pancreatic cancer cells supports the escape of pancreatic cancer cells from immunosurveillance. The present findings highlight a new dimension of MUC5AC as a functional immunosuppressive agent and its important role in pancreatic cancer progression.