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源自人骨肉瘤的降钙素反应性细胞系的特征

Characteristics of a calcitonin-responsive cell line derived from a human osteosarcoma.

作者信息

Eilon G, Perkins J, Viola M V

出版信息

Cancer Res. 1983 Aug;43(8):3763-9.

PMID:6574818
Abstract

Although the primary cell type in human osteosarcoma is usually a neoplastic osteoblast, numerous other mesenchymal cell types may coexist in the same tumor. Previously described cloned, long-term osteosarcoma cell lines have had an osteoblastic phenotype. In this report, we describe a nonosteoblastic, long-term cell line derived from an osteosarcoma in a patient with Paget's disease. The cell line (FM-2) is nontransformed in having a low saturation density and anchorage-dependent growth, and it is nontumorigenic in nude mice. Important features of its fine structure include numerous elongated mitochondria, abundant Golgi and lysosomes, and a poorly developed rough endoplasmic reticulum. The line has high levels of lysosomal enzymes (acid phosphatase and N-acetylglucosaminidase) and low levels of alkaline phosphatase. It lacks numerous macrophage markers (lysozyme, C3, Fc receptors, and M1 antigen). The FM-2 line had a dose-dependent cyclic AMP response (7-fold increase) following treatment with calcitonin but not with parathormone. In 125I-calcitonin-binding experiments, we calculated approximately 5.3 +/- 0.2 X 10(3) receptor sites/cell with a kd of 1.8 +/- 0.1 X 10(-9) M. Conditioned medium from the FM-2 line was a potent stimulator of calcium release as assayed in a 45Ca-labeled fetal rat bone organ culture. This activity was not prostaglandin, vitamin D, parathormone, or epidermal growth factor, which are known stimulators of bone resorption. The FM-2 line does not appear to be derived from an osteoblast, macrophage, or fibroblast and may represent a calcitonin-responsive bone stem cell.

摘要

尽管人类骨肉瘤中的主要细胞类型通常是肿瘤性成骨细胞,但许多其他间充质细胞类型可能在同一肿瘤中共存。先前描述的克隆化长期骨肉瘤细胞系具有成骨细胞表型。在本报告中,我们描述了一种源自佩吉特病患者骨肉瘤的非成骨细胞长期细胞系。该细胞系(FM-2)未发生转化,具有低饱和密度和锚定依赖性生长,并且在裸鼠中不具有致瘤性。其精细结构的重要特征包括大量细长的线粒体、丰富的高尔基体和溶酶体,以及发育不良的粗面内质网。该细胞系具有高水平的溶酶体酶(酸性磷酸酶和N-乙酰葡糖胺酶)和低水平的碱性磷酸酶。它缺乏许多巨噬细胞标志物(溶菌酶、C3、Fc受体和M1抗原)。用降钙素处理后,FM-2细胞系具有剂量依赖性的环磷酸腺苷反应(增加7倍),但用甲状旁腺激素处理则无此反应。在125I-降钙素结合实验中,我们计算出约5.3±0.2×10³个受体位点/细胞,解离常数为1.8±0.1×10⁻⁹M。在45Ca标记的胎鼠骨器官培养中检测发现,FM-2细胞系的条件培养基是钙释放的有效刺激物。这种活性不是已知的骨吸收刺激物前列腺素、维生素D、甲状旁腺激素或表皮生长因子。FM-2细胞系似乎不是源自成骨细胞、巨噬细胞或成纤维细胞,可能代表一种降钙素反应性骨干细胞。

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引用本文的文献

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Feasibility and barriers to rapid establishment of patient-derived primary osteosarcoma cell lines in clinical management.在临床管理中快速建立患者来源的原发性骨肉瘤细胞系的可行性及障碍
iScience. 2024 Jun 19;27(9):110251. doi: 10.1016/j.isci.2024.110251. eCollection 2024 Sep 20.
2
Human placental calcitonin receptors.人胎盘降钙素受体
Biochem J. 1988 Mar 15;250(3):877-82. doi: 10.1042/bj2500877.
3
Procalcitonin's amino-terminal cleavage peptide is a bone-cell mitogen.降钙素原的氨基末端裂解肽是一种骨细胞促分裂原。
Proc Natl Acad Sci U S A. 1989 Dec;86(23):9519-23. doi: 10.1073/pnas.86.23.9519.
4
Calcitonin (but not calcitonin gene-related peptide) increases mouse bone cell proliferation in a dose-dependent manner, and increases mouse bone formation, alone and in combination with fluoride.降钙素(而非降钙素基因相关肽)以剂量依赖方式增加小鼠骨细胞增殖,并单独或与氟化物联合使用时增加小鼠骨形成。
Calcif Tissue Int. 1989 Oct;45(4):214-21. doi: 10.1007/BF02556040.
5
Characterization of a new human osteosarcoma cell line OHS-4.一种新的人骨肉瘤细胞系OHS-4的特性分析
J Cell Biol. 1991 Aug;114(3):577-83. doi: 10.1083/jcb.114.3.577.