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恶性干细胞是导致乳腺癌容易复发的原因

电镜扫描下的乳腺癌细胞 (图)

美国科学家在乳腺癌干细胞中发现了一些基因异常,它可能是乳腺癌发生和复发的诱因。这些变异后的干细胞似乎在肿瘤中控制着细胞的功能,如果不被化疗和放疗所杀死,它们可引起癌症复发。

通过研究手术切除下来的乳腺癌肿瘤细胞,美国俄勒冈州健康科学大学的癌症中心的科学家和内科医生发现了细胞中的这些突变,该研究的论文发表在了最新一期的《Annals of Surgical Oncology》杂志上。

论文的第一作者,肿瘤外科手术部门的教授SuEllen J. Pommier说道:“通过研究比较乳腺组织中的正常细胞和突变细胞,我们可以判断出患者体内的大致状况。”

由于目前体外培养的各种乳腺相关的细胞株在生物学特征上不能准确反映正常的乳腺干细胞特性,只有通过研究这些直接从切除手术中收集到的样本,并与正常的乳腺干细胞相比,才能发现它们之间的真正差异。

这项研究证实了现在的一些临床常规治疗手段靶向杀伤这些突变的乳腺干细胞不是非常有效,因此常常无法彻底根除疾病。同时,科学家们提出了两项需要进行深入研究的领域:

1. 在新鲜的组织样本中,有超过73%的样本发现了PIK3CA/AKT1信号通路的突变,为何这远远高于以前检测的储存样本中的比例。

2. 需要进一步研究证实CD24表达在乳腺癌中的作用,之前的研究广泛认为CD24的表达缺失是乳腺癌干细胞的典型特征,但目前研究结果显示并非是所有乳腺癌干细胞均有CD24表达缺失。

Pommier教授说道:“了解这些肿瘤的生物学特性是我们的主要工作。这项研究让我们对乳腺癌干细胞有了新的了解,并且这种突变很可能发生在癌症形成的最初阶段,这对于未来开发有效的治疗手段至关重要。”

英文论文原文摘要:

Characterizing the HER2/neu Status and Metastatic Potential of Breast Cancer Stem/Progenitor Cells

Introduction
Treatment resistance, long latency, and high recurrence rates suggest that breast cancers arise from defective breast stem cells.

Hypothesis
Within cancers, subpopulations of cells will demonstrate differences in stem/progenitor potential, HER2/neu amplification, and gene expression. Related cells will be found in normal breast tissue.

Methods
ER-/PR-/HER2/neu + breast cancer cells were flow-sorted into subpopulations: (A) CD49f+ CD24−, (B) CD49f+CD24+, (C) CD49f CD24−, and (D) CD49f−CD24+. Gel matrix cell invasion, fluorescence in situ hybridization (FISH) HER2/neu amplification, and qRT-PCR gene expression were measured in all groups. Cells from sorted groups were implanted into rat brains. Resultant tumors were analyzed by immunohistochemistry (IHC) and FISH. Normal breast tissue was examined by IHC.

Results
Tumor development varied among sorted groups (25–75%), but was highest in group A. Tumor cells were mostly CD49f−CD24−, with variable fractions of other stem/progenitor cells. Tumors showed HER2/neu amplification, but fewer chromosome 17 per cell than inoculates. Group A tumors exhibited cells with normal chromosome 17 copy number and near normal HER2/neu amplification. Cell invasion was 61% higher in unsorted cells and 34–42% in sorted groups compared with controls. Sorted groups showed significantly different expression of development, proliferation, and invasion associated genes. In normal breast tissue, CD49f+ cells were identified in CD14+ CK19− basal epithelial layers of mammary glands; these were 95% CD24+ and 60% CD44+.

Conclusions
Breast cancer stem/progenitor cell populations differ in tumor-initiating potential but are not solely responsible for metastasis. Cancer stem/progenitor cells are less polyploid than cancer cells in general and may not be HER2/neu amplified. In normal breast tissue, breast stem/progenitor cell-like populations are present.

 

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