Calreticulin is highly expressed in pancreatic cancer stem-like cells.

Calreticulin is highly expressed in pancreatic cancer stem-like cells.
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DOI:
10.1111/cas.13061
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发表时间:
2016-11
期刊:
影响因子:
5.7
通讯作者:
Nagano H
Nagano H
中科院分区:
医学2区
文献类型:
--
作者:
Matsukuma S;Yoshimura K;Ueno T;Oga A;Inoue M;Watanabe Y;Kuramasu A;Fuse M;Tsunedomi R;Nagaoka S;Eguchi H;Matsui H;Shindo Y;Maeda N;Tokuhisa Y;Kawano R;Furuya-Kondo T;Itoh H;Yoshino S;Hazama S;Oka M;Nagano H

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实体瘤中的癌症干细胞样细胞(CSLC)被认为对传统化疗或分子靶向治疗具有抵抗力,并导致癌症复发和转移。在本研究中,我们的目的是鉴定胰腺 CSLC (P-CSLC) 的生物标志物。使用我们之前报道的方法从胰腺癌细胞系中生成富含 P-CSLC 的群体,并通过二维电泳和串联质谱法将其蛋白质表达谱与亲本细胞的蛋白质表达谱进行比较。结果表明,与亲本细胞相比,P-CSLC 中的伴侣蛋白钙网蛋白 (CRT) 显着上调。流式细胞术分析表明,CRT 主要位于 P-CSLC 表面,与另一种 P-CSLC 生物标志物 CD44v9 的水平无关。此外,CRThigh/CD44v9low群体中的侧群体远高于CRTlow/CD44v9high群体中的侧群体。还通过免疫组织化学方法评估了根治性切除后获得的胰腺癌组织(n = 80)中的钙网蛋白表达,并发现其与 Cox 比例风险回归模型中患者的临床病理特征和疾病结果相关。多变量分析确定 CRT 与年龄和术后治疗一样,是胰腺癌患者的独立预后因素。我们的结果表明,CRT 可以作为 P-CSLC 的生物标志物和与胰腺癌患者较差生存相关的预后因素。这种新型生物标志物可被视为癌症免疫疗法的治疗靶点。
Cancer stem‐like cells (CSLCs) in solid tumors are thought to be resistant to conventional chemotherapy or molecular targeting therapy and to contribute to cancer recurrence and metastasis. In this study, we aimed to identify a biomarker of pancreatic CSLCs (P‐CSLCs). A P‐CSLC‐enriched population was generated from pancreatic cancer cell lines using our previously reported method and its protein expression profile was compared with that of parental cells by 2‐D electrophoresis and tandem mass spectrometry. The results indicated that a chaperone protein calreticulin (CRT) was significantly upregulated in P‐CSLCs compared to parental cells. Flow cytometry analysis indicated that CRT was mostly localized to the surface of P‐CSLCs and did not correlate with the levels of CD44v9, another P‐CSLC biomarker. Furthermore, the side population in the CRThigh/CD44v9low population was much higher than that in the CRTlow/CD44v9high population. Calreticulin expression was also assessed by immunohistochemistry in pancreatic cancer tissues (n = 80) obtained after radical resection and was found to be associated with patients' clinicopathological features and disease outcomes in the Cox proportional hazard regression model. Multivariate analysis identified CRT as an independent prognostic factor for pancreatic cancer patients, along with age and postoperative therapy. Our results suggest that CRT can serve as a biomarker of P‐CSLCs and a prognostic factor associated with poorer survival of pancreatic cancer patients. This novel biomarker can be considered as a therapeutic target for cancer immunotherapy.
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