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在快速进展型胃癌模型中骨髓和外周血中肿瘤细胞的早期检测。

Early detection of tumor cells in bone marrow and peripheral blood in a fast‑progressing gastric cancer model.

机构信息

Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093‑0640, USA.

出版信息

Int J Oncol. 2021 Mar;58(3):388-396. doi: 10.3892/ijo.2021.5171. Epub 2021 Jan 12.

Abstract

Helicobacter pylori (H. pylori) infection is a major risk factor for the development of gastric cancer. The authors previously demonstrated that in mice deficient in myeloid differentiation primary response 88 (Myd88‑/‑), infection with Helicobacter felis (H. felis) a close relative of H. pylori, subsequently rapidly progressed to neoplasia. The present study examined circulating tumor cells (CTCs) by measuring the expression of cytokeratins, epithelial‑to‑mesenchymal transition (EMT)‑related markers and cancer stem cell (CSC) markers in bone marrow and peripheral blood from Myd88‑/‑ and wild‑type (WT) mice. Cytokeratins CK8/18 were detected as early as 4 months post‑infection in Myd88‑/‑ mice. By contrast, cytokeratins were not detected in WT mice even after 7 months post‑infection. The expression of Mucin‑1 (MUC1) was observed in both bone marrow and peripheral blood at different time points, suggesting its role in gastric cancer metastasis. Snail, Twist and ZEB were expressed at different levels in bone marrow and peripheral blood. The expression of these EMT‑related markers suggests the manifestation of cancer metastasis in the early stages of disease development. LGR5, CD44 and CD133 were the most prominent CSC markers detected. The detection of CSC and EMT markers along with cytokeratins does reinforce their use as biomarkers for gastric cancer metastasis. This early detection of markers suggests that CTCs leave primary site even before cancer is well established. Thus, cytokeratins, EMT, and CSCs could be used as biomarkers to detect aggressive forms of gastric cancers. This information may prove to be of significance in stratifying patients for treatment prior to the onset of severe disease‑related characteristics.

摘要

幽门螺杆菌(H. pylori)感染是胃癌发展的主要危险因素。作者先前证明,在髓样分化初级反应 88 基因(Myd88-/-)缺陷的小鼠中,感染与 H. pylori 密切相关的 Helicobacter felis(H. felis)后,肿瘤迅速进展为肿瘤。本研究通过测量骨髓和外周血中细胞角蛋白、上皮-间质转化(EMT)相关标志物和癌症干细胞(CSC)标志物的表达,检测循环肿瘤细胞(CTC)。在 Myd88-/-小鼠中,早在感染后 4 个月就检测到细胞角蛋白 CK8/18。相比之下,即使在感染后 7 个月,WT 小鼠也未检测到细胞角蛋白。在不同时间点,在骨髓和外周血中均观察到粘蛋白 1(MUC1)的表达,表明其在胃癌转移中的作用。Snail、Twist 和 ZEB 在骨髓和外周血中以不同的水平表达。这些 EMT 相关标志物的表达表明在疾病发展的早期阶段就表现出了癌症转移。LGR5、CD44 和 CD133 是检测到的最突出的 CSC 标志物。CSC 和 EMT 标志物以及细胞角蛋白的检测确实支持它们作为胃癌转移的生物标志物。这些标志物的早期检测表明,CTC 甚至在癌症尚未完全形成之前就已经离开原发部位。因此,细胞角蛋白、EMT 和 CSCs 可作为生物标志物,用于检测侵袭性胃癌。这些信息可能在疾病相关特征出现之前对患者进行分层治疗具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/141b/7864146/2bdf16d2b69a/IJO-58-03-0388-g00.jpg

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