Yi Liang, Zhou Zhi-hua, Ping Yi-fang, Chen Jian-hong, Yao Xiao-hong, Feng Hua, Lu Jia-you, Wang Ji Ming, Bian Xiu-wu
Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing, China.
Mod Pathol. 2007 Oct;20(10):1061-8. doi: 10.1038/modpathol.3800942. Epub 2007 Jul 27.
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.
实体瘤中一小部分干细胞样前体细胞与多种恶性肿瘤的组织学组成、进展、血管生成、转移、复发及耐药性相关。少突星形细胞瘤是最常见的脑混合性胶质瘤，由少突胶质细胞和星形细胞表型的混合细胞组成。鉴定和表征少突星形细胞瘤中的干细胞样前体细胞可能有助于揭示这种独特类型肿瘤的肿瘤发生机制，并有助于设计新的治疗策略。在此，通过用巢蛋白和CD133标记肿瘤切片，从原发性人间变性少突星形细胞瘤中鉴定出肿瘤干细胞样前体细胞。将肿瘤细胞在含有生长因子的干细胞培养基中进行体外培养，并测试存活的干细胞样前体细胞形成肿瘤球的能力。将肿瘤球进一步皮下注射到裸鼠体内，以观察干细胞样前体细胞对组织学组成和肿瘤进展的作用。我们发现原发性人少突星形细胞瘤组织中含有巢蛋白+/CD133+干细胞样前体细胞。这些细胞分化为具有少突胶质细胞和星形细胞特征的肿瘤细胞，并在体外形成肿瘤球，将其植入裸鼠后，生长为肿瘤结节，其中巢蛋白+/CD133+细胞的水平高于原发性肿瘤组织。这项研究首次揭示，人间变性少突星形细胞瘤含有干细胞样前体细胞，这些细胞具有神经干细胞特性并具有致瘤性。这些干细胞样前体细胞可能是人少突星形细胞瘤少突胶质细胞和星形细胞成分的来源，应被视为治疗靶点。
