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Copurification of Osteolytic and Transforming Growth Factor ß Activities Produced by Human Lung Tumor Cells Associated with Humoral Hypercalcemia of Malignancy¹

Departments of Pediatrics [T. A. L.], Biochemistry [T. A. L., S. M., D. J. B.], Medicine [S. M., J. C. J., D. J. B.], Physiology [S. M.], and Orthopedic Surgery [D. J. B.], Loma Linda University Medical School and Mineral Metabolism Laboratory, Jerry L. Pettis Veterans' Hospital, Loma Linda, California 92357

The SK-Luci-6 cell line, established from a large-cell anaplastic lung tumor of a patient with humoral hypercalcemia of malignancy (HHM), was investigated to identify osteolytic factors produced that might mediate HHM. Most HHM-associated tumors are thought to produce parathyroid hormone-related proteins or transforming growth factor (TGF) .

SK-Luci-6 cells formed s.c. tumors and induced hypercalcemia in athymic nude mice. Serum-free conditioned medium from SK-Luci-6 cultures induced bone resorption in neonatal mouse calvariae in vitro, and also contained TGF-ß activity and mitogenic activity. SK-Luci-6 cell conditioned medium did not displace [¹²⁵I]epidermal growth factor binding to cell receptors or stimulate cyclic AMP formation in rat osteosarcoma cells, suggesting that the conditioned medium did not contain TGF- or parathyroid hormone-related proteins. The osteolytic, TGF-ß, and mitogenic activities copurified in several chromatographic separations: gel filtration in acid and then in guanidine HCl; ion exchange; and reverse phase. The results suggest that in the HHM-associated SK-Luci-6 tumor, the causative osteolytic factor produced by the tumor cells is not a parathyroid hormone-related protein or TGF- but, rather, may be a TGF-ß.

¹ Supported by Medical Research Grants from the Veterans Administration.

² To whom requests for reprints should be addressed, at Research Service (151), Pettis Veterans Hospital, 11201 Benton Street, Loma Linda, CA 92357.

Received 7/12/88. Revised 9/29/88. Accepted 10/20/88.