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乳腺癌干细胞是乳腺肿瘤内具有自我更新能力以及多向分化潜能的细胞,乳腺癌的发生﹑发展、转移﹑复发与干细胞的高致瘤性、高侵袭转移性、治疗抵抗能力密切相关。深入研究乳腺癌干细胞相关细胞因子及微环境因素的调控对乳腺癌的临床靶向治疗具有重要指导意义。该文就近年来乳腺癌干细胞调控相关信号转导通路、转录因子、表观遗传调控因子以及微环境因素进行综述,探讨乳腺癌干细胞及其相关信号因子作为乳腺癌治疗靶点的潜在价值,为临床靶向治疗乳腺癌提供新方向。 相似文献
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除骨髓移植外,以化疗为主的急性白血病治愈率很低,尤其因耐药复发的难治性急性白血病不能治愈的原因是患者体内存在一群具有自我更新能力的白血病干细胞。虽然这些细胞数量极少,但可自我更新,具有很强的增殖潜能,在白血病发生和复发过程中起着关键性作用。白血病干细胞的存在和增殖受细胞表面分子、细胞调控信号通路、细胞自我更新信号通路与骨髓微环境等多因素影响,其中,细胞自我更新信号通路及其相关基因表达在维系白血病干细胞生物学特征方面发挥着重要作用 相似文献
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肿瘤干细胞是存在于肿瘤组织中的具有自我更新、增殖、分化的部分细胞群,对肿瘤的发生、发展有十分重要的作用. 肿瘤干细胞特异的表面分子及其异常活化的信号通路,是其区别于其他肿瘤细胞的特性.寻找和鉴定特异的肿瘤干细胞的表面标志物,从而识别肿瘤组织中的肿瘤干细胞,并进行相关信号调控机制研究,是肿瘤早期诊断及肿瘤干细胞靶向治疗的关键. 本文简要概述了肿瘤干细胞相关的表面标志物及信号通路的研究进展,旨在为进一步开展针对肿瘤干细胞的抗体靶向治疗提供新思路. 相似文献
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Wnt信号通路与神经干细胞 总被引:2,自引:0,他引:2
神经干细胞增殖、分化机制的研究为神经系统疾病治疗提供了新的途径,具有巨大的潜在应用价值和理论研究意义。业已发现,Wnt信号通路对神经干细胞的增殖发挥着决定性作用,但新近的研究却表明Wnt信号能够明显促进神经干细胞向神经元分化,这种不同的表现可能与神经干细胞的内在特点、周围环境及靶基因的不同有关。本文试从Wnt信号通路及其在调控神经干细胞的增殖、分化中的作用加以综述。 相似文献
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目的:探究纳米形貌诱导间充质干细胞(MSC)分化中的作用以及相关分子机制。方法:利用阳极氧化法制备二氧化钛纳米管形貌,使用qRT-PCR技术,RNA-seq技术,分析接种在纳米形貌表面的间充质干细胞的基因表达情况。并筛选对成骨相关的信号通路中的成员,观察他们基因上调或下调情况。结果:在钛金属表面构建出了纳米形貌,利用实时定量PCR确定了成骨相关的基因:碱性磷酸酶(ALP),骨桥蛋白(OPN)和骨钙素(OCN)相比没有纳米形貌的钛片上培养的细胞均发生上调。通过对这些基因相关的成骨信号通路进行转录组数据分析(筛选基因P<0.05),发现在BMP2信号通路中的相关蛋白基因表达没有太大变化,同时Notch以及Wnt非经典信号通路中相关蛋白基因发生较为明显变化。结论:通过分析间充质干细胞成骨分化相关基因,以及转录组数据分析表明在纳米形貌诱导BMSC分化过程中,相对于平坦的表面,纳米形貌启动了Notch以及非经典的Wnt信号通路,因此表现出更加优良的促成骨分化的效果。 相似文献
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骨髓干细胞包括造血干细胞(HSCs)和间充质干细胞(MSCs),骨髓间充质干细胞(BMSCs)是一类具有自我更新、增殖和多向分化能力的细胞,具有不对称分裂和无限增殖的特点。在肝细胞生长因子(HGF)的作用下,BMSCs可以分化为肝细胞,参与诱导这一分化过程的相关信号通路包括NF-kB信号通路、Notch信号通路、MAPK信号通路、Wnt信号通路和STAT3信号通路。文章主要就BMSCs分化为肝细胞的相关信号通路进行了综述。 相似文献
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Fatemeh Vahidian Hamed Mohammadi Mohammad Ali-Hasanzadeh Afshin Derakhshani Masoud Mostaan Maryam Hemmatzadeh Behzad Baradaran 《Journal of cellular physiology》2019,234(4):3294-3306
MicroRNAs (miRNAs) can control cancer and cancer stem cells (CSCs), and this topic has drawn immense attention recently. Stem cells are a tiny population of a bulk of tumor cells that have enormous potential in expansion and metastasis of the tumor. miRNA have a crucial role in the management of the function of stem cells. This role is to either promote or suppress the tumor. In this review, we investigated the function and different characteristics of CSCs and function of the miRNAs that are related to them. We also demonstrated the role and efficacy of these miRNAs in breast cancer and breast cancer stem cells (BCSC). Eventually, we revealed the metastasis, tumor formation, and their role in the apoptosis process. Also, the therapeutic potential of miRNA as an effective method for the treatment of BCSC was described. Extensive research is required to investigate the employment or suppression of these miRNAs for therapeutics approached in different cancers in the future. 相似文献
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Breast cancer angiogenesis is elicited and regulated by a number of factors including the Notch signaling. Notch receptors and ligands are expressed in breast cancer cells as well as in the stromal compartment and have been implicated in carcinogenesis. Signals exchanged between neighboring cells through the Notch pathway can amplify and consolidate molecular differences, which eventually dictate cell fates. Notch signaling and its crosstalk with many signaling pathways play an important role in breast cancer cell growth, migration, invasion, metastasis and angiogenesis, as well as cancer stem cell (CSC) self-renewal. Therefore, significant attention has been paid in recent years toward the development of clinically useful antagonists of Notch signaling. Better understanding of the structure, function and regulation of Notch intracellular signaling pathways, as well as its complex crosstalk with other oncogenic signals in breast cancer cells will be essential to ensure rational design and application of new combinatory therapeutic strategies. Novel opportunities have emerged from the discovery of Notch crosstalk with inflammatory and angiogenic cytokines and their links to CSCs. Combinatory treatments with drugs designed to prevent Notch oncogenic signal crosstalk may be advantageous over λ secretase inhibitors (GSIs) alone. In this review, we focus on the more recent advancements in our knowledge of aberrant Notch signaling contributing to breast cancer angiogenesis, as well as its crosstalk with other factors contributing to angiogenesis and CSCs. 相似文献
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Yuk Wah Chan Chun So Ka Long Yau Kung Chun Chiu Xiya Wang Franky Leung Chan Suk Ying Tsang 《Journal of cellular physiology》2020,235(10):6794-6807
Adipose-derived stem cells (ADSCs) are a type of mesenchymal stem cells isolated from adipose tissue and have the ability to differentiate into adipogenic, osteogenic, and chondrogenic lineages. Despite their great therapeutic potentials, previous studies showed that ADSCs could enhance the proliferation and metastatic potential of breast cancer cells (BCCs). In this study, we found that ADSCs fused with BCCs spontaneously, while breast cancer stem cell (CSC) markers CD44+CD24-/lowEpCAM+ were enriched in this fusion population. We further assessed the fusion hybrid by multicolor DNA FISH and mouse xenograft assays. Only single nucleus was observed in the fusion hybrid, confirming that it was a synkaryon. In vivo mouse xenograft assay indicated that the tumorigenic potential of the fusion hybrid was significantly higher than that of the parent tumorigenic triple-negative BCC line MDA-MB-231. We had compared the fusion efficiency between two BCC lines, the CD44-rich MDA-MB-231 and the CD44-poor MCF-7, with ADSCs. Interestingly, we found that the fusion efficiency was much higher between MDA-MB-231 and ADSCs, suggesting that a potential mechanism of cell fusion may lie in the dissimilarity between these two cell lines. The cell fusion efficiency was hampered by knocking down the CD44. Altogether, our findings suggest that CD44-mediated cell fusion could be a potential mechanism for generating CSCs. 相似文献
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Hippo信号通路是调控器官大小和肿瘤发生发展的关键通路,近年来受到广泛的关注。TAZ/YAP作为哺乳动物中Hippo信号通路两个核心下游效应分子,通过Hippo信号通路依赖性和非依赖性的机制受到细胞内外信号的严密调控。除了参与正常乳腺组织发育,Hippo信号通路还在人乳腺癌细胞的增殖、分化、凋亡、迁移、侵袭、上皮-间质转化和干性维持等多个过程中起着关键性作用。本文总结了Hippo信号通路的调控机制和调节信号,阐述了Hippo信号通路异常在乳腺癌发生发展中的作用,并讨论了其在乳腺癌中作为治疗靶点的临床策略。 相似文献
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Dorothea Sonja Schott Monika Pizon Ulrich Pachmann Katharina Pachmann Rainer Schobert Andrea Wittig Matthias Mäurer 《Translational oncology》2021,14(3):101009
Background: There is an unmet need to identify biomarkers that directly reflect response to adjuvant radiotherapy (RT). Circulating epithelial tumor cells (CETCs) represent the liquid component of solid tumors and are responsible for metastatic relapse. CETC subsets with cancer stem cell characteristics, circulating cancer stem cells (cCSCs), play a pivotal role in the metastatic cascade. Monitoring the most aggressive subpopulation of CETCs could reflect the aggressiveness of the remaining tumor burden. There is limited data on the detection and monitoring changes in CETC and cCSC numbers during RT in early breast cancer.Methods: CETC numbers were analyzed prior to, at midterm and at the end of RT in 52 primary non-metastatic breast cancer patients. Hormone receptor status was determined in CETCs prior to and at the end of RT. For the identification of cCSCs cell suspensions from the peripheral blood of patients were cultured in vitro under conditions favoring growth of tumorspheres.Results: Hormone receptor status in CETCs before RT was comparable to that in primary tumor tissue. Prior to RT numbers of CETCs correlated with aggressiveness of primary tumors. cCSCs could be successfully identified and monitored during RT. Prior to RT patients treated with neoadjuvant chemotherapy had significantly higher numbers of CETCs and tumorspheres compared to patients after adjuvant chemotherapy. During RT, the number of CETCs decreased continuously in patients after neoadjuvant chemotherapy but not after adjuvant chemotherapy.Conclusion: Monitoring the number of CETCs and the CETC subset with cancer stem cell properties during RT may provide additional clinically useful prognostic information. 相似文献