Doublecortin-like kinase 1 is elevated serologically in pancreatic ductal adenocarcinoma and widely expressed on circulating tumor cells.
Doublecortin-like kinase 1 is elevated serologically in pancreatic ductal adenocarcinoma and widely expressed on circulating tumor cells.
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DOI：
10.1371/journal.pone.0118933
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Houchen CW
中科院分区：
文献类型：
--
作者：
Qu D;Johnson J;Chandrakesan P;Weygant N;May R;Aiello N;Rhim A;Zhao L;Zheng W;Lightfoot S;Pant S;Irvan J;Postier R;Hocker J;Hanas JS;Ali N;Sureban SM;An G;Schlosser MJ;Stanger B;Houchen CW
双皮质素样激酶1 （DCLK1）是一种公认的胰腺干细胞标志物，在胰腺癌、结直肠癌和许多其他实体肿瘤中表达上调。它在小鼠肠道肿瘤模型中标记肿瘤干细胞。在这里，我们试图确定DCLK1蛋白是否可以在胰腺癌患者的血液中检测到，以及是否可以定量评估其在存档血清样本中的水平。采用DCLK1特异性ELISA、western blotting和免疫组织化学分析方法检测胰腺导管腺癌（pancreatic ductal adenocarcinoma， PDAC）患者和胰腺癌小鼠模型的肿瘤组织中DCLK1在血清中的表达水平和染色强度。与健康志愿者（正常对照）相比，PDAC早期（I期和II期）血清中DCLK1水平升高。在III/IV期和正常对照组之间没有观察到差异。在切除的手术组织中，基质细胞中的DCLK1表达强度明显高于肿瘤上皮细胞。从KPCY小鼠中分离出循环肿瘤细胞，约52%的循环肿瘤细胞Dclk1染色阳性。KPC小鼠血清中Dclk1水平也升高。我们之前已经证明DCLK1在调节上皮间充质转化（EMT）中发挥潜在作用。鉴于EMT来源的干细胞在癌症进展和转移中的作用日益得到认可，我们假设DCLK1可能有助于转移过程。综上所述，我们的研究结果表明，DCLK1血清水平和DCLK1阳性循环肿瘤细胞应进一步评估其潜在的诊断和预后意义。
Doublecortin-like kinase 1 (DCLK1) is a putative pancreatic stem cell marker and is upregulated in pancreatic cancer, colorectal cancer, and many other solid tumors. It marks tumor stem cells in mouse models of intestinal neoplasia. Here we sought to determine whether DCLK1 protein can be detected in the bloodstream and if its levels in archived serum samples could be quantitatively assessed in pancreatic cancer patients. DCLK1 specific ELISA, western blotting, and immunohistochemical analyses were used to determine expression levels in the serum and staining intensity in archived tumor tissues of pancreatic ductal adenocarcinoma (PDAC) patients and in pancreatic cancer mouse models. DCLK1 levels in the serum were elevated in early stages of PDAC (stages I and II) compared to healthy volunteers (normal controls). No differences were observed between stages III/IV and normal controls. In resected surgical tissues, DCLK1 expression intensity in the stromal cells was significantly higher than that observed in tumor epithelial cells. Circulating tumor cells were isolated from KPCY mice and approximately 52% of these cells were positive for Dclk1 staining. Dclk1 levels in the serum of KPC mice were also elevated. We have previously demonstrated that DCLK1 plays a potential role in regulating epithelial mesenchymal transition (EMT). Given the increasingly recognized role of EMT derived stem cells in cancer progression and metastasis, we hypothesize that DCLK1 may contribute to the metastatic process. Taken together, our results suggest that DCLK1 serum levels and DCLK1 positive circulating tumor cells should be further assessed for their potential diagnostic and prognostic significance.
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影响因子：
5.7
作者：
Balagurunathan, Yoganand;Morse, David L.;Hostetter, Galen;Shanmugam, Vijayalakshmi;Stafford, Phillip;Shack, Sonsoles;Pearson, John;Trissal, Maria;Demeure, Michael J.;Von Hoff, Daniel D.;Hruby, Victor J.;GillieS, Robert J.;Han, Haiyong
通讯作者：
Han, Haiyong
影响因子：
4
作者：
Bao, Bin;Wang, Zhiwei;Ali, Shadan;Kong, Dejuan;Banerjee, Sanjeev;Ahmad, Aamir;Li, Yiwei;Azmi, Asfar S.;Miele, Lucio;Sarkar, Fazlul H.
通讯作者：
Sarkar, Fazlul H.
影响因子：
8
作者：
通讯作者：
--
影响因子：
29.4
作者：
Delgiorno KE;Hall JC;Takeuchi KK;Pan FC;Halbrook CJ;Washington MK;Olive KP;Spence JR;Sipos B;Wright CV;Wells JM;Crawford HC
通讯作者：
Crawford HC
影响因子：
11.2
作者：
Li, Chenwei;Heidt, David G.;Simeone, Diane M.
通讯作者：
Simeone, Diane M.