Lectins identify glycan biomarkers on glioblastoma-derived cancer stem cells.
Lectins identify glycan biomarkers on glioblastoma-derived cancer stem cells.
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凝集素可识别胶质母细胞瘤来源的癌症干细胞上的聚糖生物标志物。
DOI：
10.1089/scd.2011.0369
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发表时间：
2012
影响因子：
4
通讯作者：
Nash,
中科院分区：
文献类型：
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作者：
Tucker-Burden,Carol;Chappa,Prasanthi;Krishnamoorthy,Malini;Gerwe,BrianA;Scharer,ChristopherD;Heimburg-Molinaro,Jamie;Harris,Wayne;Usta,SümeyraNaz;Eilertson,CarmenD;Hadjipanayis,ConstantinosG;Stice,StevenL;Brat,DanielJ;Nash,
胶质母细胞瘤（GBM）是一种高度侵袭性的原发性脑肿瘤，预后不良。尽管有积极的手术治疗，放疗和化疗，几乎所有的患者在2年内死于疾病。几项研究支持脑肿瘤培养物中存在干细胞样细胞，这些细胞是CD 133阳性的，能够自我更新，并产生肿瘤内发现的所有细胞类型，可能使生长永久化。CD 133是一种被广泛接受的胶质瘤源性癌症干细胞的标志物;然而，它的可靠性受到质疑，因此需要这种生物学上重要的亚群的其他标识符。我们使用了一组20凝集素，以确定在未分化的神经胶质瘤源性干细胞和分化细胞的糖萼中发现的聚糖表达的差异。特异性识别α-N-乙酰半乳糖胺（GalNAc）和α-N-乙酰葡糖胺（GlcNAc）的双标记凝集素根据细胞分化状态差异性结合至细胞表面。GalNAc和GlcNAc在未分化细胞的表面上高度表达，并且在分化的12天持续时间内显示出显著降低的表达。此外，GalNAc识别凝集素双花扁豆凝集素能够从未分选的肿瘤储备中特异性选择和分选神经胶质瘤衍生的干细胞群，并且该亚群具有与体外CD 133+细胞相似的增殖特性，并且还具有体内肿瘤形成能力。我们对单个小脑GBM的初步结果表明，GalNAc和GlcNAc是用于识别胶质瘤源性干细胞的新型生物标志物，可用于从未分选的细胞群中分离癌症干细胞，从而创建用于研究或临床测试的新细胞系。
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 lectinDolichos biflorusagglutinin 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.