Identification of glycoprotein markers for pancreatic cancer CD24+CD44+ stem-like cells using nano-LC-MS/MS and tissue microarray.
Identification of glycoprotein markers for pancreatic cancer CD24+CD44+ stem-like cells using nano-LC-MS/MS and tissue microarray.
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DOI：
10.1021/pr201059g
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发表时间：
2012-04-06
影响因子：
4.4
通讯作者：
Lubman, David M.
中科院分区：
文献类型：
--
作者：
Zhu, Jianhui;He, Jintang;Liu, Yashu;Simeone, Diane M.;Lubman, David M.
关键词：
胰腺癌的特点是由于缺乏早期症状、广泛转移和对化疗/放疗的高抵抗力而导致诊断较晚。最近，胰腺癌中的细胞亚群，称为癌症干细胞（CSC），已被表征和假定为胰腺癌的驱动因素，并负责转移扩散。因此，对胰腺CSC的进一步研究对于确定这种令人沮丧的疾病的新诊断标志物和治疗靶点特别重要。在此，胰腺癌干细胞样CD 24 + CD 44+细胞的恶性表型是从人胰腺癌细胞系（PANC-1）中分离的，并且与CD 24 − CD 44+细胞相比，其侵袭能力提高了4倍。使用凝集素微阵列和纳米LC-MS/MS，我们确定了这两个亚群之间的差异表达的糖蛋白。凝集素微阵列分析显示，岩藻糖和半乳糖特异性凝集素，UEA-1和DBA，分别表现出明显的强结合CD 24 + CD 44+细胞。结果表明，共鉴定出17个差异表达的糖蛋白，包括上调的Cytokeratin 8/CK 8、Integrin β1/CD 29、ICAM 1/CD 54和Ribophorin 2/RPN 2，下调的Amp N/CD 13。组织芯片的免疫组化分析表明，CD 24与晚期胰腺癌显着相关，和RPN 2只与CD 24在一小群CD 24阳性细胞共表达。然而，CD 13表达随着肿瘤进展沿着显著降低，在早期肿瘤中，其优先存在于导管细胞和血管的顶膜上。我们的研究结果表明，这些糖蛋白可能为胰腺癌提供潜在的治疗靶点和有前途的预后标志物。
Pancreatic adenocarcinoma is characterized by late diagnosis due to lack of early symptoms, extensive metastasis, and high resistance to chemo/radiation therapy. Recently, a subpopulation of cells within pancreatic cancers, termed cancer stem cells (CSCs), has been characterized and postulated to be the drivers for pancreatic cancer and responsible for metastatic spread. Further studies on pancreatic CSCs are therefore of particular importance to identify novel diagnosis markers and therapeutic targets for this dismal disease. Herein, the malignant phenotype of pancreatic cancer stem-like CD24+CD44+ cells was isolated from a human pancreatic carcinoma cell line (PANC-1), and demonstrated 4-fold increased invasion ability compared to CD24−CD44+ cells. Using lectin microarray and nano LC-MS/MS, we identified a differentially expressed set of glycoproteins between these two subpopulations. Lectin microarray analysis revealed that fucose- and galactose-specific lectins, UEA-1 and DBA respectively, exhibit distinctly strong binding to CD24+CD44+ cells. The glycoproteins extracted by multi-lectin affinity chromatography were consequently analyzed by LC-MS/MS. 17 differentially expressed glycoproteins were identified, including upregulated Cytokeratin 8/CK8, Integrin β1/CD29, ICAM1/CD54 and Ribophorin 2/RPN2, and downregulated Aminopeptidase N/CD13. Immunohistochemical analysis of tissue microarrays showed that CD24 was significantly associated with late-stage pancreatic adenocarcinomas, and RPN2 was exclusively coexpressed with CD24 in a small population of CD24-positive cells. However, CD13 expression was dramatically decreased along with tumor progression, preferentially present on the apical membrane of ductal cells and vessels in early-stage tumors. Our findings suggest that these glycoproteins may provide potential therapeutic targets and promising prognostic markers for pancreatic cancer.
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影响因子：
6.4
作者：
Grzesiak, John J.;Cao, Hop S. Tran;Burton, Douglas W.;Kaushal, Sharmeela;Vargas, Fabian;Clopton, Paul;Snyder, Cynthia S.;Deftos, Leonard J.;Hoffman, Robert M.;Bouvet, Michael
通讯作者：
Bouvet, Michael
影响因子：
11.2
作者：
Galli, R;Binda, E;Vescovi, A
通讯作者：
Vescovi, A
CD13 在炎症和肿瘤组织血管中的表达增强
影响因子：
3.2
作者：
Di Matteo, Paola;Arrigoni, Gian Luigi;Rizzardi, Gian-Paolo
通讯作者：
Rizzardi, Gian-Paolo
影响因子：
82.9
作者：
Honma, Kimi;Iwao-Koizumi, Kyoko;Ochiya, Takahiro
通讯作者：
Ochiya, Takahiro
影响因子：
3
作者：
Hirabayashi, J
通讯作者：
Hirabayashi, J