Copurification of osteolytic and transforming growth factor beta activities produced by human lung tumor cells associated with humoral hypercalcemia of malignancy.
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) alpha. 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-beta 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-alpha or parathyroid hormone-related proteins. The osteolytic, TGF-beta, 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-alpha but, rather, may be a TGF-beta.
Linkhart
T A
TA
Department of Pediatrics, Loma Linda University Medical School, California.
Mohan
S
S
Jennings
J C
JC
Baylink
D J
DJ
D000818:Animals; D002118:Calcium / Q000032:analysis; D002460:Cell Line; D002642:Chick Embryo; D000242:Cyclic AMP / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000378:metabolism*; D008175:Lung Neoplasms / Q000032:analysis* / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010014:Osteolysis; D012516:Osteosarcoma / Q000378:metabolism; D015291:Transforming Growth Factors / Q000302:isolation & purification*
D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D000242:Cyclic AMP; D002118:Calcium