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《生命科学研究》2019,(6)
存在于骨髓中的间充质干细胞(bone marrow mesenchymal stem cells,BMSCs,也称为间充质基质细胞)可以被募集到肿瘤部位并构成肿瘤微环境。细胞代谢在癌症进展中起重要作用。在癌症微环境中间充质细胞和肿瘤细胞发生代谢方式的转变。然而,尚不清楚肿瘤细胞和BMSCs细胞的相互作用如何影响细胞代谢和肿瘤进展。在本研究中,通过将BMSCs和小鼠肺癌细胞LLC细胞共同注射到C57BL/6小鼠,构建了皮下瘤模型;随后在原位瘤分离BMSCs和LLC细胞,进行RNA测序,以获得肿瘤微环境下BMSCs和LLC细胞的转录组。结果显示BMSCs中上调的基因富集于代谢途径。进一步根据差异表达的分子构建相互作用网路,发现BMSCs网络中的核心预测途径是代谢途径、MAPK信号通路和HIF-1信号通路。然而,在肿瘤微环境中LLC细胞的代谢途径受到抑制。体内动物实验证实抑制糖酵解可以减少荷瘤小鼠肿瘤的生长。以上结果提示,BMSCs增加了糖酵解,通过反式Warburg效应促进癌细胞的生长,在肿瘤微环境下BMSCs的代谢重编程影响肿瘤细胞的转归。 相似文献
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Na Li Yu Yang Miao Ding Weidan Huang Huaguang Li Jing Ye Jing Xiao Xiliang Zha Haineng Xu 《Molecular biotechnology》2014,56(12):1079-1088
Cancer stem cells (CSCs) are a subset of cancer cells that play key roles in metastasis and cancer relapse. The elimination of CSCs is very important during cancer therapy. To develop drugs that target CSCs, the isolation and identification of putative CSCs are required. Some of the characteristics of CSCs are assessed by cell survival assays. In such experiments, the density of the cells seeded on the plates may affect the experimental results, leading to potentially inaccurate conclusions. In this study, a new assay to facilitate the characterization of CSCs has been developed by stable transfection of GFP, using the A549 lung cancer cell line as a model. A putative CSC line, A549 sphere cells, was obtained by culturing A549 cells in ultra-low dishes in serum-free medium. To ensure that the putative CSCs were grown under the same conditions as the A549–GFP cells and were not affected by the number of cells seeded, A549 sphere cells were mixed with GFP stably transfected A549 (A549–GFP) cells. The mixture was subjected to flow cytometry assay and inverted fluorescence microscopy to detect changes in the proportion of GFP-positive cells after treatment. A549 sphere cells had a slower proliferation rate and an improved chemoresistance. They also showed differentiation ability. This work suggests that mixing GFP stably transfected cancer cells with putative CSCs may facilitate the identification of CSCs, making it convenient for studies of targeted CSCs. 相似文献
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成体干细胞来源广泛,无伦理争议,成为近几年的关注热点。研究表明以骨髓来源的间充质干细胞为代表的成体干细胞具有较强的多系分化潜能,可以广泛的参与包括肺在内的受损组织的修复与重建。在动物实验中已观察到,供体来源的成体干细胞可以定向分化为受损肺组织的多种功能细胞,并且有抑制纤维化等病变产生的能力。在本文中,回顾了近年来与肺损伤重建和疾病治疗相关的干细胞研究的最新进展,并探讨了成体干细胞治疗肺疾病与损伤的临床应用前景。 相似文献
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Isocitrate dehydrogenase 1 and 2 (IDH1/2) are enzymes recurrently mutated in various types of cancer, including glioma, cholangiocarcinoma, chondrosarcoma, and acute myeloid leukemia. Mutant IDH1/2 induce a block in differentiation and thereby contribute to the stemness and oncogenesis of their cells of origin. Recently, small-molecule inhibitors of mutant IDH1/2 have been Food and Drug Administration–approved for the treatment of IDH1/2-mutated acute myeloid leukemia. These inhibitors decrease the stemness of the targeted IDH1/2-mutated cancer cells and induce their differentiation to more mature cells. In this review, we elucidate the mechanisms by which mutant IDH1/2 induce a block in differentiation and the biological and clinical effects of the release into differentiation by mutant-IDH1/2 inhibitors. (J Histochem Cytochem 70:83–97, 2022) 相似文献
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最近的一项研究报导,采用流式细胞仪分选技术从人胃癌细胞株中分离出CD44+胃癌干细胞. 20~30×103个CD44+细胞入NOD/SCID 鼠腹部皮下和胃浆膜下能形成胃癌移植瘤, 100×103个CD44-的细胞入NOD/SCID 鼠体内不形成肿瘤.采用无血清、无粘附间质的干细胞体外培养方法,发现CD44+的细胞能形成肿瘤微球体,具有自我更新能力,而CD44-的细胞则不形成球形克隆.上述的实验结果说明,在人胃癌细胞株中存在胃癌肿瘤干细胞.据此可以相信,胃癌干细胞是胃癌细胞中具有自我更新及分化潜能的一小群细胞,不能被目前的化疗、放疗等抗癌治疗措施所杀灭,是胃癌术后复发、肿瘤进展扩散转移的根源.胃癌干细胞可能来源于骨髓干细胞.随着对胃癌肿瘤干细胞生物学研究的深入,必将为胃癌的临床诊断和治疗提供新的策略. 相似文献
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近年来,肿瘤干细胞学说作为肿瘤发生发展的重要原因获得越来越多的认可。肿瘤干细胞是指肿瘤中存在的含量极少、具有无限增殖潜能的干细胞样肿瘤细胞,它们能自我更新、分化、迁徙,是导致肿瘤发生、发展、转移和耐药的重要原因。卵巢癌也可能是卵巢癌干细胞所致的疾病。卵巢癌干细胞的分离鉴定正处于起始阶段,针对卵巢癌干细胞的靶向治疗可能在卵巢癌治疗中具有重要作用,为临床彻底治愈卵巢癌带来希望。 相似文献
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Breast Cancer Stem Cell Therapeutics,Multiple Strategies Versus Using Engineered Mesenchymal Stem Cells With Notch Inhibitory Properties: Possibilities and Perspectives
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Relapse cases of cancers are more vigorous and difficult to control due to the preponderance of cancer stem cells (CSCs). Such CSCs that had been otherwise dormant during the first incidence of cancer gradually appear as radiochemoresistant cancer cells. Hence, cancer therapeutics aimed at CSCs would be an effective strategy for mitigating the cancers during relapse. Alternatively, CSC therapy can also be proposed as an adjuvant therapy, along‐with the conventional therapies. As regenerative stem cells (RSCs) are known for their trophic effects, anti‐tumorogenicity, and better migration toward an injury site, this review aims to address the use of adult stem cells such as dental pulp derived; cord blood derived pure populations of regenerative stem cells for targeting CSCs. Indeed, pro‐tumorogenicity of RSCs is of concern and hence has also been dealt with in relation to breast CSC therapeutics. Furthermore, as notch signaling pathways are upregulated in breast cancers, and anti‐notch antibody based and sh‐RNA based therapies are already in the market, this review focuses the possibilities of engineering RSCs to express notch inhibitory proteins for breast CSC therapeutics. Also, we have drawn a comparison among various possibilities of breast CSC therapeutics, about, notch1 inhibition. J. Cell. Biochem. 119: 141–149, 2018. © 2017 Wiley Periodicals, Inc. 相似文献
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Ping Wang Quanli Gao Zhenhe Suo Else Munthe Steinar Solberg Liwei Ma Mengyu Wang Nomdo Anton Christiaan Westerdaal Gunnar Kvalheim Gustav Gaudernack 《PloS one》2013,8(3)
Lung cancer (LC) with its different subtypes is generally known as a therapy resistant cancer with the highest morbidity rate worldwide. Therapy resistance of a tumor is thought to be related to cancer stem cells (CSCs) within the tumors. There have been indications that the lung cancer is propagated and maintained by a small population of CSCs. To study this question we established a panel of 15 primary lung cancer cell lines (PLCCLs) from 20 fresh primary tumors using a robust serum-free culture system. We subsequently focused on identification of lung CSCs by studying these cell lines derived from 4 representative lung cancer subtypes such as small cell lung cancer (SCLC), large cell carcinoma (LCC), squamous cell carcinoma (SCC) and adenocarcinoma (AC). We identified a small population of cells strongly positive for CD44 (CD44high) and a main population which was either weakly positive or negative for CD44 (CD44low/−). Co-expression of CD90 further narrowed down the putative stem cell population in PLCCLs from SCLC and LCC as spheroid-forming cells were mainly found within the CD44highCD90+ sub-population. Moreover, these CD44highCD90+ cells revealed mesenchymal morphology, increased expression of mesenchymal markers N-Cadherin and Vimentin, increased mRNA levels of the embryonic stem cell related genes Nanog and Oct4 and increased resistance to irradiation compared to other sub-populations studied, suggesting the CD44highCD90+ population a good candidate for the lung CSCs. Both CD44highCD90+ and CD44highCD90− cells in the PLCCL derived from SCC formed spheroids, whereas the CD44low/− cells were lacking this potential. These results indicate that CD44highCD90+ sub-population may represent CSCs in SCLC and LCC, whereas in SCC lung cancer subtype, CSC potentials were found within the CD44high sub-population. 相似文献
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Lu Zhang Wenmin Chen Suling Liu Ceshi Chen 《International journal of biological sciences》2023,19(2):552
The potential roles of breast cancer stem cells (BCSCs) in tumor initiation and recurrence have been recognized for many decades. Due to their strong capacity for self-renewal and differentiation, BCSCs are the major reasons for poor clinical outcomes and low therapeutic response. Several hypotheses on the origin of cancer stem cells have been proposed, including critical gene mutations in stem cells, dedifferentiation of somatic cells, and cell plasticity remodeling by epithelial-mesenchymal transition (EMT) and the tumor microenvironment. Moreover, the tumor microenvironment, including cellular components and cytokines, modulates the self-renewal and therapeutic resistance of BCSCs. Small molecules, antibodies, and chimeric antigen receptor (CAR)-T cells targeting BCSCs have been developed, and their applications in combination with conventional therapies are undergoing clinical trials. In this review, we focus on the features of BCSCs, emphasize the major factors and tumor environment that regulate the stemness of BCSCs, and discuss potential BCSC-targeting therapies. 相似文献
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肿瘤干细胞存在于多种类型肿瘤中,并与肿瘤的发生发展密切相关。肿瘤干细胞和胚胎干细胞在生物学特征上存在许多共同点,如自我更新,多潜能性分化等等。然而,肿瘤干细胞和胚胎干细胞又存在很大差异,主要表现在耐药性、致瘤力和转移活性上。肿瘤干细胞在临床研究中具有不可替代的重要性,然而其分子水平上的调节机制尚未被完整揭示。作为内源性非编码小RNA的一部分,miRNAs在细胞发生发展的调节过程中扮演着重要角色。大量研究表明,miRNAs参与肿瘤干细胞的调节,并参与肿瘤的发生与进展。探索miRNAs在肿瘤干细胞基因表达调控中的作用及作用机制,有助于肿瘤特异性生物学标志物及治疗靶点的确定。本文就miRNAs与肿瘤干细胞调节的相关研究进展进行综述。 相似文献