In the formation of bone metastasis, osteoclastic bone resorption is necessary before the expansion of tumor cells from bone marrow to bone, and several cytokines, which possess osteoclast-stimulating activity, could be involved in this step. In this paper, we describe a bone metastasis model in nude mice using human lung squamous cell carcinoma-derived cells (HARA), in which the parathyroid hormone-related protein (PTHrP) gene, one of the most potent osteoclast-activating factors, is strongly expressed. The injection of HARA cells (1 × 105) into the left cardiac ventricle resulted in tumor colonies exclusively in the skeletal system at 4 and/or 8 weeks after inoculation. An anti-PTHrP antibody injected via a tail vein reduced the incidence of bone metastases, number of tumor colonies, and tumor volume after the inoculation of HARA cells. The injection of another line of human lung squamous cell carcinoma-derived cells (QG-56), in which the PTHrP gene is not expressed, resulted in no bone metastasis. These findings suggest that PTHrP plays an important role in the formation of bone metastasis.

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Supported in part by a Grant-in-Aid for the 2nd-Term Comprehensive 10-Year Strategy of Cancer Control from the Ministry of Health and Welfare of Japan and a Grant-in-Aid from the Fukuoka Cancer Society (1995).

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©1996 American Association for Cancer Research.
1996
American Association for Cancer Research, Inc.