The utility and limitations of glycosylated human CD133 epitopes in defining cancer stem cells

Human CD133 (human prominin-1), a five transmembrane domain glycoprotein, was originally identified as a cell surface antigen present on CD34+ hematopoietic stem cells. Although the biological function of CD133 is not well understood, antibodies to CD133 epitopes have been widely used to purify hematopoietic stem and progenitor cells. The cancer stem cell (CSC) hypothesis postulates that a rare population of tumor cells possessing increased capacities for self-renewal and tumor initiation is responsible for maintaining the growth of neoplastic tissue. The expression of the CD133 epitopes, AC133 and AC141, has been shown to define a subpopulation of brain tumor cells with significantly increased capacity for tumor initiation in xenograft models. Following the discovery of the AC133/AC141+ population of brain tumor stem cells, the AC133 and AC141 epitopes have been extensively used as markers for purifying CSCs in other solid tumors. There are, however, several issues associated with the use of the AC133 and AC141 CD133 epitopes as markers for CSCs. The antibodies routinely used for purification of AC133 and AC141-positive cells target poorly characterized glycosylated epitopes of uncertain specificity. Discordant expression of the AC133 and AC141 epitopes has been observed, and the epitopes can be absent despite the presence of CD133 protein. In addition, CD133 expression has recently been shown to be modulated by oxygen levels. These factors, in combination with the uncertain biological role of CD133, suggest that the use of CD133 expression as a marker for CSCs should be critically evaluated in each new experimental system and highlight the need for additional CSC surface markers that are directly involved in maintaining CSC properties.     

Isolation of cancer stem cells from transformed human mesenchymal stem cell line F6

Cancer stem cells (CSCs) have the characteristics of self-renewal, unlimited proliferation, and initiating new tumors. However, the origin of CSCs is still controversial. F6, a tumor cell line transformed from human fetal mesenchymal stem cells, was established in our previous study. Whether CSCs exist in this mutated cell line remains unclear. In the present study, we isolated CSCs from F6 cells based on CD133 expression using flow cytometry and investigated the biological characteristics of CD133+ F6 cells (F6-CD133+). We observed that the F6-CD133+ cells grew faster and had a higher capacity of colony formation than the F6-CD133− cells and parental F6 cells in vitro. In addition, F6-CD133+ cells had a higher tumorigenic ability than F6-CD133− cells in vivo since 1,000 F6-CD133+ cells were able to form tumors in nude mice. Cell viability assay revealed that F6-CD133+ cells were more sensitive to cisplatin while less to 5-fluorouracil. Furthermore, gene expression profile analysis showed that there were 673 differentially expressed genes between F6-CD133+ and F6-CD133− cells, many of which were involved in key cell signaling pathways. Taken together, our findings confirm that F6 cells contain a population of CSCs that contribute to its heterogeneity and tumorigenic potential, indicating that transformed stem cells could be the source of CSCs, and targeting this population may lead to more effective tumor treatments.     

Clinical and biological implications of CD133-positive and CD133-negative cells in glioblastomas

A number of recent reports have demonstrated that only CD133-positive cancer cells of glioblastoma multiforme (GBM) have tumor-initiating potential. These findings raise an attractive hypothesis that GBMs can be cured by eradicating CD133-positive cancer stem cells (CSCs), which are a small portion of GBM cells. However, as GBMs are known to possess various genetic alterations, GBMs might harbor heterogeneous CSCs with different genetic alterations. Here, we compared the clinical characteristics of two GBM patient groups divided according to CD133-positive cell ratios. The CD133-low GBMs showed more invasive growth and gene expression profiles characteristic of mesenchymal or proliferative subtypes, whereas the CD133-high GBMs showed features of cortical and well-demarcated tumors and gene expressions typical of proneuronal subtype. Both CD133-positive and CD133-negative cells purified from four out of six GBM patients produced typical GBM tumor masses in NOD-SCID brains, whereas brain mass from CD133-negative cells showed more proliferative and angiogenic features compared to that from CD133-positive cells. Our results suggest, in contrast to previous reports that only CD133-positive cells of GBMs can initiate tumor formation in vivo CD133-negative cells also possess tumor-initiating potential, which is indicative of complexity in the identification of cancer cells for therapeutic targeting.     

星形胶质细胞瘤干细胞的体外分离、培养与鉴定

背景：肿瘤干细胞理论认为肿瘤中存在一小部分具有无限增殖潜能和自我更新能力,能够分化为成熟细胞表型的干细胞样细胞,对肿瘤发生、增殖、侵袭起关键作用。 目的：建立体外分离、培养与鉴定星形胶质细胞瘤干细胞的方法。 方法：采用直接培养法分离培养星形胶质细胞瘤干细胞。参照神经干细胞培养条件,进行体外培养。观察其增殖、分化并进行巢蛋白、CD133免疫细胞化学鉴定和诱导分化后神经元特异性烯醇化酶、胶质纤维酸性蛋白及O4免疫细胞化学鉴定。 结果与结论：培养7-10 d,可形成大量悬浮生长巢蛋白及CD133免疫阳性的神经球,经诱导分化后细胞呈神经元特异性烯醇化酶、胶质纤维酸性蛋白或O4免疫阳性。提示星形胶质细胞瘤中存在具有神经干细胞特性的肿瘤干细胞。CD133和巢蛋白是星形胶质细胞瘤干细胞重要的表面标记,可以用于星形胶质细胞瘤干细胞的分离。     

MAGE-A3 is highly expressed in a cancer stem cell-like side population of bladder cancer cells

Cancer stem cells (CSCs), which have the abilities of tumor-initiating, self-renewal and differentiation, are thought to cause post-therapeutic recurrence and the progression of cancer. However, CSCs are commonly resistant to current cancer therapies including chemotherapy and radiotherapy. In this study, we isolated cancer stem celllike side population (SP) cells from human bladder cancer cell line SW780 by a flow cytometry-based SP technique. SP cells were only about 3.6% of SW780 cells and showed higher expression of ATP-binding cassette sub-family G member 2 (ABCG2) and CD133. In vitro assay of tumor sphere growth as well as in vivo assay of xenograft transplantation confirmed the higher tumorigenicity of isolated SP cells. These data indicated that SP cells were enriched with CSCs of bladder cancer. Furthermore, we determined the expression of melanoma antigen family A, 3 (MAGEA3), one of the most studied cancer testis (CT) antigens, in these SP and main population (MP) cells derived from SW780 cells. SW780 SP cells representing CSCs of bladder cancer showed an up-regulated expression of MAGE-A3 and a positive coexpression of MAGE-A3 and CD133, indicating that MAGE-A3 was a novel CT antigen preferentially expressed in the CSCs of bladder cancer. In summary, our findings confirmed the existence of cancer stem cell-like SP cells in bladder cancer cells, and further indicated that MAGE-A3 is a novel CSC antigen and therefore may serve as an immunotherapeutic target for CSCs of bladder cancer.     

Role of ursolic acid chalcone,a synthetic analogue of ursolic acid,in inhibiting the properties of CD133+ sphere-forming cells in liver stem cells

The expression of CD133 decreases with differentiation of tumor cell, indicating that CD133 is a specific marker for isolation and identification of CSCs. In the present study the effect of Ursolic acid chalcone (UAC) on CD133⁺ hepatocellular carcinoma cell (HCC CSCs) differentiation, their self-renewal, tumorigenic capacity and sensitivity to chemotherapeutic drugs was studied. The results demonstrated that UAC inhibits the expression of CD133⁺ in a dose and time-dependent manner in PLC/PRF/5 and Huh7 HCC cells. The inhibition was significant at 50 μM and on day 8. The percentage of CD133⁺ cells decreased from an initial 59.3% in PLC/PRF/5 to 37.1% and 78.2% in Huh7 to 59.2% on treatment with UAC. There was inhibition of Oct4, Tert, Bmi1, β-catenin, ABCG2, and tumor sphere-related gene Ep300. In addition it also decreased number of CK19-positive cells and increased number of CK8/18-positive cells. UAC treatment caused a decrease in self-renewal capability and increase in sensitivity to doxorubicin and vincristine drugs in CD133⁺ HCC CSCs. Therefore, UAC can be a potent therapeutic agent to target differentiation of CSC in HCC.     

脑肿瘤干细胞的研究现状

背景：在脑肿瘤中存在一种具有自我更新、无限增殖与多向分化能力的细胞,即脑肿瘤干细胞。脑肿瘤干细胞被认为是脑肿瘤发生、发展、转移与复发的根源。 目的：总结和探讨脑肿瘤干细胞的研究现状。 方法：以“脑肿瘤、脑肿瘤干细胞”为检索词,应该计算机检索Pubmed 数据库1977-01/2011-07的相关文章,并查阅与干细胞及脑肿瘤干细胞实验有关的书籍,对资料进行初审,选取符合要求的有关文章共32 篇。 结果与结论：在恶性脑肿瘤中存在脑肿瘤干细胞。脑肿瘤干细胞是恶性脑肿瘤发生、发展、转移及复发的根源,其表达特异性的CD133、Nestin蛋白和ABC转运体。目前已经获得了分离脑肿瘤干细胞的简便方法。CD133阳性的肿瘤干细胞所占的比例与脑肿瘤的恶性程度呈正相关,可作为预后诊断指标之一。      

Lectins identify glycan biomarkers on glioblastoma-derived cancer stem cells

Glioblastoma (GBM) is a highly aggressive primary brain tumor with a poor prognosis. Despite aggressive therapy with surgery, radiotherapy, and chemotherapy, nearly all patients succumb to disease within 2 years. Several studies have supported the presence of stem-like cells in brain tumor cultures that are CD133-positive, are capable of self-renewal, and give rise to all cell types found within the tumor, potentially perpetuating growth. CD133 is a widely accepted marker for glioma-derived cancer stem cells; however, its reliability has been questioned, creating a need for other identifiers of this biologically important subpopulation. We used a panel of 20 lectins to identify differences in glycan expression found in the glycocalyx of undifferentiated glioma-derived stem cells and differentiated cells that arise from them. Fluorescently labeled lectins that specifically recognize α-N-acetylgalactosamine (GalNAc) and α-N-acetylglucosamine (GlcNAc) differentially bound to the cell surface based on the state of cellular differentiation. GalNAc and GlcNAc were highly expressed on the surface of undifferentiated cells and showed markedly reduced expression over a 12-day duration of differentiation. Additionally, the GalNAc-recognizing lectin Dolichos biflorus agglutinin was capable of specifically selecting and sorting glioma-derived stem cell populations from an unsorted tumor stock and this subpopulation had proliferative properties similar to CD133(+) cells in vitro and also had tumor-forming capability in vivo. Our preliminary results on a single cerebellar GBM suggest that GalNAc and GlcNAc are novel biomarkers for identifying glioma-derived stem cells and can be used to isolate cancer stem cells from unsorted cell populations, thereby creating new cell lines for research or clinical testing.     

Isolation and characterization of stem cell-like precursor cells from primary human anaplastic oligoastrocytoma.

A small population of stem cell-like precursors in solid tumors are linked to histological composition, progression, angiogenesis, metastasis, recurrence and drug resistance of a variety of malignant tumors. Oligoastrocytoma is the most common brain mixed glioma composed of mixed cells of oligodendroglial and astrocytic phenotypes. Identification and characterization of stem cell-like precursors in oligoastrocytoma may shed light on the oncogenesis of this unique type of tumor and assist in the design of novel therapeutic strategy. Here, tumor stem cell-like precursors were identified from primary human anaplastic oligoastrocytomas by labeling of the tumor sections with nestin and CD133. Tumor cells were cultured in vitro in stem cell medium with growth factors and the capacity of the surviving stem cell-like precursors to form tumor spheres was tested. The tumor spheres were further injected subcutaneously into nude mice to observe the contribution of stem cell-like precursors to histological composition and tumor progression. We found that primary human oligoastrocytoma tissues contained nestin+/CD133+ stem cell-like precursors. These cells differentiated into tumor cells with both oligodendroglial and astrocytic characteristics and formed tumor spheres in vitro, which upon implantation in nude mice, grew into tumor nodules containing nestin+/CD133+ cells at levels higher than in the primary tumor tissues. This study revealed for the first time that anaplastic human oligoastrocytomas contained stem cell-like precursors, which exhibit neural stem cell properties with tumorigenicity. These stem cell-like precursors may be responsible for the oligodendroglial and astrocytic components of human oligoastrocytoma and should be considered as therapeutic targets.     

Expression of cancer stem cell markers ALDH1, CD44 and CD133 in primary tumor and lymph node metastasis of gastric cancer

Gastric cancer (GC) is one of the most common malignancies worldwide. Recently, cancer stem cells (CSCs) in tumors were found to possess the ability to sustain tumor self-renewal, initiate tumor progression, and possibly also contribute to cancer metastasis. We immunohistochemically examined expression and distribution of representative CSC markers ALDH1, CD44, and CD133 in primary tumors and lymph node metastasis of GC. Among 190 GC primary tumors, 104 (55%) were positive for ALDH1, 117 (62%) were positive for CD44, and 18 (9%) were positive for CD133. Expression of these three CSC markers was significantly associated with advanced clinicopathologic factors. Patients with CD44- and CD133-positive GC had a poorer survival rate than patients with CD44- and CD133-negative GC (CD44: P < 0.001, CD133: P= 0.006). Univariate and multivariate Cox proportional hazards analysis revealed tumor node metastasis stage, CD44 expression, and CD133 expression to be independent predictors of survival in patients with GC. Comparison of CSC markers in primary and metastatic sites showed ALDH1 positivity to be significantly higher in diffuse-type lymph node metastasis than in the primary tumor (P < 0.001). These results indicate that these CSC markers are important in tumor invasion and metastasis and may be good markers indicating long-term survival in patients with GC.     

肿瘤干细胞的分离培养及生物学特性

背景：肿瘤干细胞是一类具有自我更新能力、不定分化潜能的种子细胞,可以形成不同分化程度的肿瘤细胞, 是恶性肿瘤不断生长、复发转移、无法被传统的放化疗方法彻底杀死的根源。 目的：总结肿瘤干细胞的分离培养及其生物学特性。 方法：由作者采用电子检索的方式,在万方数据库中检索以“肿瘤干细胞,分离培养,生物学特性” 为中文关键词,计算机检索1990-01/2010-12有关肿瘤干细胞的分离培养及生物学特性的文章,经检索共查到相关文献45篇。经阅读标题、摘要、全文后,排除内容重复、普通综述、Meta分析类文章后,筛选纳入22篇文献进行评价。 结果与结论：在肺癌、胰腺癌、结肠癌、肝细胞癌、神经系统肿瘤等多种脏器肿瘤中,CD133被作为鉴定肿瘤干细胞的特异性标记物之一。巢蛋白、波形蛋白和CD117在神经系统肿瘤干细胞中有表达。CD44及内皮素转化酶在肺癌肿瘤干细胞中的表达具有意义。CD44和CD24可作为分选人胰腺癌细胞株PANC-1中肿瘤干细胞的表面标志。而CD166在大肠癌肿瘤干细胞中高表达。     

Spontaneous in vitro transformation of adult neural precursors into stem-like cancer cells

Recent studies have found that cellular self-renewal capacity in brain cancer is heterogeneous, with only stem-like cells having this property. A link between adult stem cells and cancer stem cells remains, however, to be shown. Here, we describe the emergence of cancer stem-like cells from in vitro cultured brain stem cells. Adult rat subventricular zone (SVZ) stem cells transformed into tumorigenic cell lines after expansion in vitro . These cell lines maintained characteristic features of stem-like cells expressing Nestin, Musashi-1 and CD133, but continued to proliferate upon differentiation induction. Karyotyping detected multiple acquired chromosomal aberrations, and syngeneic transplantation into the brain of adult rats resulted in malignant tumor formation. Tumors revealed streak necrosis and displayed a neural as well as an undifferentiated phenotype. Deficient downregulation of platelet-derived growth factor (PDGF) receptor alpha was identified as candidate mechanism for tumor cell proliferation, and its knockdown by siRNA resulted in a reduction of cell growth. Our data point to adult brain precursor cells to be transformed in malignancies. Furthermore, in vitro expansion of adult neural stem cells, which will be mandatory for therapeutic strategies in neurological disorders, also harbors the risk for amplifying precursor cells with acquired genetic abnormalities and induction of malignant tumors after transplantation.     

A possible interplay between HR-HPV and stemness in tumor development: an in vivo investigation of CD133 as a putative marker of cancer stem cell in HPV18-infected KB cell line

High-risk HPVs (HR-HPVs) are DNA viruses considered as primary etiologic factors in malignancies of the low female genital tract. Their presence has also been documented in oropharyngeal and laryngeal cancers. However, HPV infection is considered a necessary but not sufficient cause of tumoral development; meantime, increasing evidences on the tumorigenic role of cancer stem cells (CSCs) have been documented in the literature. CSCs represent a small subpopulation of neoplastic cells with self-renewal potential, capable of maintaining tumor growth and cell differentiation, also involved in metastatic process, recurrence, and resistance to chemotherapeutic agents. In the present study, performed on KB cell lines, we evaluated the tumor forming potential of CSCs, and their relationship with the HPV infection status. We started our study by identifying the most aggressive cell line on the minimal number of cells being able of growth in vivo in a model of athymic nude mice (BALB/c nu/nu). We used an oral-derived KB cell line separated in the KB-CD133+ and KB-CD133- populations, by using immunomagnetic beads and fluorescence-activated cell sorting (FACS). The separated populations were injected in athymic nude mice (BALB/c nu/nu). Xenograft tumors have been analyzed for tumor size, CD133 expression by immunohistochemistry (IHC) and for DNA HR-HPV integration by in situ hybridization (ISH), comparing CD133-enriched xenograft tumors versus the CD133 non-enriched ones. On standard conditions, the KB cell line has a poor population of glycosylated CD133 marker (<5.0%) when investigated with antibodies versus CD133, and more specifically its glycosylated epitope (AC133). Enriched CD133 KB cells possess a higher capacity of tumor growth in xenograft models of nude mice when compared to KB CD133-negative cells. We observed that the AC133 epitope, extensively used to purifying hematopoietic stem cells, is able to select an epithelial subpopulation of cancer stem cells with aggressive behavior. We retain that CD133 may be a useful target in anticancer strategies including pharmacological and immunological therapies.     

Enhanced expression of stem cell markers and drug resistance in sphere-forming non-small cell lung cancer cells

There is growing evidence suggesting that cancer stem cells (CSCs) are playing critical roles in tumor progression, metastasis and drug resistance. However, the role of CSCs in non-small cell lung cancer (NSCLC) remains elusive. In this study, we enriched for stem-like cells from tumor spheres derived from NSCLC cell line A549 cultured in serum-free medium. Our results showed that sphere-derived cells expressed various stem cell markers such as CD44, CD133, Sox2 and Oct4. Compared with the corresponding cells in monolayer cultures, sphere-derived cells showed marked morphologic changes and increased expression of the stem cell markers CD133. Furthermore, we found that sphere-derived cells exhibited increased proliferation, cell-cycle progression as well as drug-resistant properties as compared to A549 adherent cells. Consistently, expression of several drug resistance proteins, including lung resistance-related protein (LRP), glutathion-S-transferase-π (GST-π) and multidrug resistance proteins-1 (MRP1) were all significantly enhanced in sphere-derived cells. These results indicate the enrichment of CSCs in sphere cultures and support their role in regulating drug resistance in NSCLC.     

Persistence of CD133+ cells in human and mouse glioma cell lines: detailed characterization of GL261 glioma cells with cancer stem cell-like properties

The concept of cancer stem cells suggests that there are malignant stem-like cells within a tumor that are responsible for tumor renewal and resistance to cytotoxic therapies. Studies have identified glioma stem-like cells that extrude Hoechst 33342 dye, representing a double-negative "side population" (SP) thought to be selectively resistant to drug therapy. A CD133+ stem cell-like subpopulation has been isolated from a human glioma that was enriched for tumor-initiating cells. It is unknown whether CD133+ cells with similar phenotype persist in established glioma cell lines, or if CD133 is a marker of glioma stem-like cells in rodents. We investigated whether CD133+ and SP cells existed in the GL261 cell line, a syngeneic mouse glioma model that is widely used for preclinical and translational research. Intracerebral injection of less than 100 CD133+ GL261 cells formed tumors, whereas it required 10,000 CD133(-) cells to initiate a tumor. CD133+ GL261 cells expressed nestin, formed tumor spheres with high frequency, and differentiated into glial and neuronal-like cells. Similar to GL261, seven human glioma cell lines analyzed also contained a rare CD133+ population. Surprisingly, we found that CD133+ GL261 cells did not reside in the SP, nor did the majority ( approximately 94%) of CD133+ human glioma cells. These results demonstrate that the expression of CD133 in murine glioma cells is associated with enhanced tumorigenicity and a stem-like phenotype. This study also reveals a previously unrecognized level of heterogeneity in glioma cell lines, exposing several populations of cells that have characteristics of cancer stem cells.     

人鼻咽癌CD133+干细胞的生物学特性及意义**

背景：有研究表明肿瘤细胞株中存在肿瘤干细胞,是肿瘤复发、转移的根源,但人鼻咽癌细胞株CNE-2中肿瘤干细胞的表达及生物学特性至今少有报道。 目的：观察人鼻咽癌CD133+干细胞生物学特性及意义。 方法：采用流式细胞仪检测人鼻咽癌细胞株CNE-2中CD133的表达情况。免疫磁珠分选技术获得人鼻咽癌CD133+干细胞,分别采用无血清培养法、CCK-8法、平板克隆形成试验及裸鼠体内成瘤实验检测CD133+干细胞的体外增殖及体内成瘤能力,并将其与CD133-及未分选鼻咽癌细胞进行比较,以了解CD133+干细胞的生物学特性。 结果与结论：免疫磁珠富集的CD133+细胞在无血清培养基中呈悬浮生长,并可以形成肿瘤干细胞球。CD133+细胞与CD133-细胞比较具有较高的克隆形成能力(P < 0.01);CD133+细胞在裸鼠体内的成瘤率高于CD133-细胞(P < 0.05)。结果证实,鼻咽癌CD133+干细胞能在体外分离培养,形成干细胞球,增殖能力强,在裸鼠体内具有极强的成瘤能力。 关键词：鼻咽癌;肿瘤干细胞;增殖;生物学特性;干细胞培养 doi:10.3969/j.issn.1673-8225.2012.06.013     

人肺癌NCI-H446细胞生成肿瘤干细胞球

目的 探索人肺癌NCI-H446细胞系干细胞球体的培养,并鉴定其生物学特性.方法 用无血清培养基培养人肺癌NCI-H446细胞得到肿瘤细胞球.将肿瘤细胞球传代扩增,并用含血清培养基培养促使其分化;四甲基偶氮唑盐(MTT)比色检测肿瘤球和普通NCI-H446细胞的增殖能力,并将肿瘤球和普通NCI-H446细胞分别植入裸鼠皮下,观察肿瘤形成;Transwell侵袭实验检测肿瘤球和普通NCI-H446细胞的侵袭能力的不同;流式细胞术检测CD133、CD44在肿瘤球和普通NCI-H446细胞中的表达,并筛选细胞表面标志物.结果 在无血清培养基中,人肺癌NCI-H446细胞可以形成少量的肿瘤细胞球,并显示很强的自我更新和增殖能力,在含血清环境中能够诱导肿瘤球分化而贴壁生长;在动物实验中,接种5×105个细胞时,肿瘤球细胞较普通NCI-H446细胞显示更强的致瘤能力;在侵袭实验中,肿瘤球细胞的侵袭能力高于普通NCI-H446细胞;干细胞标志物CD133及CD44在肿瘤球细胞的表达较普通NCI-H446细胞明显增高.结论 人肺癌细胞NCI-H446中存在癌干细胞,且可以通过无血清培养、分离和富集.     

CD133<Superscript>+</Superscript> single cell-derived progenies of colorectal cancer cell line SW480 with different invasive and metastatic potential

Single cell progenies (SCPs) inherit biological properties from their isogenetic mother cells. If a single cancer cell can give rise to progenies, which can be passaged sustainably in vitro and produce tumor in xenotransplantation, the cell should be cancer initiating cell. CD133 (Prominin-1, Prom1) is the marker of human colorectal cancer (CRC) stem cells and probably a marker of metastatic cancer stem cells (CSCs). Thirty-three SCPs of CRC cell line SW480 were isolated by limited dilution methods, thirty of which are CD133 positive and three negative. All of the CD133⁺ SCPs are tumorigenic, and the subcutaneous tumors expanded rapidly, while only 1 of 3 CD133⁻ SCPs developed a minimal tumor in nude mice. Orthotopic transplantation experiments showed that CD133⁺ SCPs possessed heterogeneity in intestinal wall invasion, lymph node and liver metastases. CD133⁺ SCPs varied in cell growth, invasive ability, epithelial-mesenchymal-transition and expression of CSCs markers (CD133, CD44, and CXCR4) associated with metastatic potential. CD133⁻ SCPs did not produce secondary transplanted tumor, intestinal invasion and metastasis. The results indicated CD133⁺ subpopulation of SW480 SCPs bear heterogeneous invasive and metastatic ability, and CRC-CSCs might be a heterogeous subpopulation.     

脑肿瘤干细胞来源及表面标记物研究的新进展

背景：随着对脑肿瘤研究逐步深化,肿瘤干细胞被发现在肿瘤生长、发展、复发和转移中起着不可或缺的独特作用。 目的：综述脑肿瘤干细胞的来源、生物学特性以及研究进展。 方法：应用计算机检索1998-01/2010-01万方数据库相关文章,检索词“脑肿瘤干细胞”,并限定文章语言种类为中文。同时计算机检索1998-01/2010-01 ELSEVIER数据库相关文章,检索词“brain tumor stem cells,BTCTs”,并限定文章语言种类为English。共检索到文献198篇,最终纳入符合标准的文献21篇。 结果与结论：脑肿瘤干细胞可能来源于神经干细胞的突变,具有自我更新和多向分化潜能,CD133和Nestin是目前应用得最多的肿瘤干细胞表面标记物,脑肿瘤干细胞的研究对阐明脑肿瘤发生机制、生物学行为及临床治疗、预后判断都具有重要意义。