Characterization and functional analysis of a slow cycling stem cell-like subpopulation in pancreas adenocarcinoma.
Characterization and functional analysis of a slow cycling stem cell-like subpopulation in pancreas adenocarcinoma.
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胰腺腺癌中缓慢循环干细胞样亚群的表征和功能分析。
DOI：
10.1007/s10585-009-9260-0
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发表时间：
2009
影响因子：
4
通讯作者：
Krauss, Stefan
中科院分区：
文献类型：
--
作者：
Dembinski, Jennifer L.;Krauss, Stefan
有证据表明，包括胰腺癌在内的多种肿瘤在对肿瘤形成、进展和转移至关重要的参数方面表现出异质性。了解实体瘤的异质性越来越多地提供了大量新的诊断和治疗方法。在这项研究中，一个特别的重点是确定一个干细胞样，慢循环肿瘤细胞在胰腺癌细胞系的亚群。使用标记保留技术，在BxPC-3和Panc03.27细胞系中鉴定并进一步评价了慢循环细胞亚群（DiI+/SCC）。这些缓慢循环的细胞设法保留亲脂性标记染料DiI，而大部分细胞（>94%）没有。DiI+/SCC群体仅显示出与CSC标志物CD 24 +/CD 44+、CD 133+和ALDH的部分重叠，但它们在化疗治疗中存活，并且能够重建初始的异质性肿瘤细胞群体。DiI+/SCC与其非标记保留、更快循环的细胞（DiI−/FCC）相比，表现出更高的侵袭潜力。它们还具有增加的致瘤潜力和类似于经历上皮向间质转化（EMT）的细胞的形态变化。通过真实的时间PCR对DiI+/SCC细胞的分析揭示了Hedgehog/TGFβ途径的指示成分的选择性上调，以及EGFR的下调，结合EMT中暗示的关键成分的转变。目前的研究结果提供了一个扩大的机制的理解，关联肿瘤启动潜力与循环速度和EMT在胰腺癌细胞系。本文的在线版本（doi：10.1007/s10585-009-9260-0）包含补充材料，可供授权用户使用。
Evidence suggests that multiple tumors, including pancreatic adenocarcinoma, display heterogeneity in parameters that are critical for tumor formation, progression and metastasis. Understanding heterogeneity in solid tumors is increasingly providing a plethora of new diagnostic and therapeutic approaches. In this study, a particular focus was put on identifying a subpopulation of stem cell-like, slow cycling tumor cells in a pancreas adenocarcinoma cell lines. Using a label retention technique a subpopulation of slow cycling cells (DiI+/SCC) was identified and further evaluated in the BxPC-3 and Panc03.27 cell lines. These slowly cycling cells managed to retain the lipophilic labeling dye DiI, while the bulk of the cells (>94%) did not. The DiI+/SCC population, showed only a partial overlap with the CSC markers CD24+/CD44+, CD133+ and ALDH but they survived chemotherapeutic treatment, and were able to recreate the initial heterogeneous tumor cell population. DiI+/SCCs exhibited an increased invasive potential as compared with their non-label retaining, faster cycling cells (DiI−/FCC). They also had increased tumorigenic potential and morphological changes resembling cells that have undergone an epithelial to mesenchymal transition (EMT). Analysis of DiI+/SCC cells by real time PCR revealed a selective up-regulation of tell tale components of the Hedgehog/TGFβ pathways, as well as a down-regulation of EGFR, combined with a shift in crucial components implied in EMT. The presented findings offer an expanded mechanistic understanding that associates tumor initiating potential with cycling speed and EMT in pancreatic cancer cell lines. The online version of this article (doi:10.1007/s10585-009-9260-0) contains supplementary material, which is available to authorized users.
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