A murine model of experimental metastasis to bone and bone marrow

• Published in: Cancer research (Chicago, Ill.) Vol. 48; no. 23; pp. 6876 - 6881
• Main Authors: ARGUELLO, F, BAGGS, R. B, FRANTZ, C. N
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-12-1988
• Subjects: Animal tumors. Experimental tumors; Animals; Biological and medical sciences; Bone and Bones - pathology; Bone Marrow Diseases - pathology; Bone Neoplasms - secondary; Disease Models, Animal; Experimental tumors, general aspects; Female; Medical sciences; Melanoma - pathology; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Tumors; Animal model; Pathogenesis; Rodentia; Metastasis; Intracardiac administration; Vertebrata; Mammalia; Mouse; B16-Melanoma; Bone marrow; Tumor; Metastatic; Bone; Tumor cell
• ISSN: 0008-5472; 1538-7445

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.