Department of Orthopedic Surgery, Macy Pavillion, New York Medical College, Valhalla, NY, 10595, USA.
Clin Orthop Relat Res. 2011 Oct;469(10):2895-904. doi: 10.1007/s11999-011-1946-3. Epub 2011 Jun 16.
Osteosarcomas are the most common solid malignant bone tumors, but little is known of their origin. The embryonal rest hypothesis views cancer cells as arising from committed progenitor stem cells in each tissue. Adult tissue contains primitive stem cells that retain the ability to differentiate across dermal lines, raising the possibility that the stem cell of origin of cancers may be from a more primitive stem cell than a progenitor.
QUESTIONS/PURPOSES: Can osteosarcoma cells, when cultured under conditions used for multipotent stem cells, be induced to differentiate into multiple phenotypes, including those of the three different dermal lineages: mesodermal, ectodermal, and endodermal?
One rat and one human osteosarcoma cell line were cultured and treated with concentrations of 0, 10(-10), 10(-9), 10(-8), 10(-7), and 10(-6) mol/L dexamethasone for 5 weeks. Seventeen phenotypes were assayed either by tissue-specific histochemical stains or antibodies to tissue-specific proteins. Each phenotype was tested across all dexamethasone concentrations for each cell line and each phenotype was tested in three separate experiments with induction by dexamethasone
Rat osteosarcoma (ROS) 17/2.8 and human osteosarcoma cell line U-2 show the appearance of cells that have markers for (1) mesodermal phenotypes such as bone, cartilage, skeletal muscle, and endothelial cells, (2) ectodermal phenotypes such as astrocytes, oligodendrocytes, neurons, and keratinocytes, and (3) an endodermal phenotype, hepatocytes. This indicates osteosarcomas are composed, at least in part, of primitive stem cells capable of differentiating into tissues from all three dermal lineages.
If osteosarcomas arise from primitive stem cells, then treatment of osteosarcomas with exogenous differentiation agents may cause the stem cells to differentiate, thus halting their proliferation and stopping tumor growth.
骨肉瘤是最常见的实体恶性骨肿瘤，但人们对其起源知之甚少。胚胎残余假说认为癌细胞起源于每个组织中已定向的祖细胞干细胞。成体组织中存在原始干细胞，这些干细胞保留着跨皮线分化的能力，这就增加了这样一种可能性，即癌症的原始干细胞可能比祖细胞更原始。
问题/目的：在用于多能干细胞的培养条件下，骨肉瘤细胞是否可以被诱导分化为多种表型，包括三个不同皮线系：中胚层、外胚层和内胚层的表型？
培养一株大鼠骨肉瘤细胞系和一株人骨肉瘤细胞系，并分别用浓度为 0、10(-10)、10(-9)、10(-8)、10(-7)和 10(-6)mol/L 的地塞米松处理 5 周。通过组织特异性组织化学染色或组织特异性蛋白抗体检测 17 种表型。每种表型均在两种细胞系的所有地塞米松浓度下进行检测，每种表型在三种不同的地塞米松诱导实验中进行检测。
大鼠骨肉瘤（ROS）17/2.8 细胞和人骨肉瘤细胞系 U-2 显示出具有以下特征的细胞出现：（1）中胚层表型，如骨、软骨、骨骼肌和内皮细胞；（2）外胚层表型，如星形胶质细胞、少突胶质细胞、神经元和角质形成细胞；（3）内胚层表型，如肝细胞。这表明骨肉瘤至少部分由原始干细胞组成，这些原始干细胞能够分化为来自三个皮线系的组织。
如果骨肉瘤起源于原始干细胞，那么用外源性分化剂治疗骨肉瘤可能会导致干细胞分化，从而阻止其增殖并停止肿瘤生长。
