A murine model of experimental metastasis to bone and bone marrow.

A murine model of experimental metastasis to bone and bone marrow.
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发表时间:
1988-12
期刊:
影响因子:
11.2
通讯作者:
F. Arguello;R. Baggs;C. Frantz
F. Arguello;R. Baggs;C. Frantz
中科院分区:
医学1区
文献类型:
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作者:
F. Arguello;R. Baggs;C. Frantz

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骨是人类癌症转移的常见部位。了解骨转移发病机制的一个主要障碍是缺乏合适的动物模型。在本文中,我们描述了一种动物模型,其中B16黑色素瘤细胞注射在左心室可重复地定殖小鼠骨骼系统的特定位点。注射10(5)个细胞导致大多数器官(包括骨骼系统)中出现黑色素肿瘤集落。注射10(4)个或更少的细胞导致实验转移几乎完全限于骨骼系统和卵巢。相比之下,静脉注射10(5)个细胞仅在肺中产生肿瘤集落。左心脏注射10(2)个细胞引起骨定植,但静脉注射相同数量的细胞不会定植在肺中。随着注射细胞数量的增加,具有肿瘤集落的骨骼数量也增加。骨中的黑色素肿瘤集落特征性地分布在长骨的干骺端和扁骨的外周。大多数动物由于脊柱骨转移压迫脊髓而发生截瘫。骨肿瘤定植仅发生在含有造血骨髓的骨区域。这表明注射的肿瘤细胞在造血骨髓环境中寄宿、存活,并生长以破坏邻近的骨。这种转移到骨的实验模型将有助于将来研究骨和骨髓转移的病理生理学和治疗。
Bone is a common site of metastasis in human cancer. A major impediment to understanding the pathogenesis of bone metastasis has been the lack of an appropriate animal model. In this paper, we describe an animal model in which B16 melanoma cells injected in the left cardiac ventricle reproducibly colonize specific sites of the skeletal system of mice. Injection of 10(5) cells resulted in melanotic tumor colonies in most organs, including the skeletal system. Injection of 10(4) or fewer cells resulted in experimental metastasis almost entirely restricted to the skeletal system and ovary. In contrast, i.v. injection of 10(5) cells resulted in tumor colonies in the lung only. Left cardiac injection of 10(2) cells caused bone colonization, but the same number of cells injected i.v. did not colonize the lung. The number of bones with tumor colonies increased with increasing number of cells injected. Melanotic tumor colonies in the bone were characteristically distributed in the metaphysis of long bones and in the periphery of flat bones. Most animals developed paraplegia due to spinal cord compression by bony metastasis to the spine. Tumor colonization of bone occurred only in regions of bone containing hematopoietic bone marrow. This suggests that the injected tumor cells lodge, survive in the hematopoietic bone marrow environment, and grow to destroy adjacent bone. This experimental model of metastasis to bone will facilitate future studies of the pathophysiology and treatment of bone and bone marrow metastasis.