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Squamous Cell Carcinomas Often Produce More Than a Single Bone Resorption-Stimulating Factor: Role of Inter leukin-1α*

1990; Oxford University Press; Volume: 127; Issue: 6 Linguagem: Inglês

10.1210/endo-127-6-3061

1945-7170

Romana A. Nowak, Nancy E. Morrison, D L Goad, Edwin V. Gaffney, A H Tashjian,

Biomarkers in Disease Mechanisms

Several cultured human squamous cell carcinoma cell lines (SCC-4, SCC-12B2, SCC-12F2, EC-GI-10, and BEN) and one normal keratinocyte line (Epy-1) were investigated for the production of bone resorption-stimulating activity (BRSA). Conditioned medium (CM) from each of the six cell lines stimulated bone resorption in neonatal mouse calvariae in culture. The BRSA of SCC-12F2 and EC-GI-10 was inhibited completely by antibody to interleukin-1α (IL-1α), whereas the BRSA in CM from the BEN, SCC-4, SCC-12B2, and Epy-1 cell lines was only partially inhibited by anti-IL-la. Addition of indomethacin to the calvarial cultures also partially inhibited the BRSA from EC-GI-10, SCC-4, SCC-12B2, and Epy-1 cells; the BRSA from BEN and SCC-12F2 cells was inhibited completely by indomethacin. cAMP production by calvariae was determined after a 60-min incubation with CM. CM from EC-GI-10, BEN, SCC-4, and Epy-1 stimulated cAMP production by bone. Preincubation of CM from BEN, EC-GI-10, SCC-4, and Epy-1 cells with two antisera against PTH-related protein [PTHrP; one specific for two PTHrP-(l-141*>, the other recognizing both PTHrP-(l-40) and PTHrP-(l-141)] completely inhibited the cAMP-stimulating activity. Using specific enzymelinked immunosorbent assays for IL-la and IL-1/3, IL-la was measured in CM of the SCC-4, SCC-12B2, SCC-12F2, and Epy-1 cell lines. IL-1/3 was undetectable (<0.1 ng/ml) in CM from all cell lines. Our findings indicate that the BRSA secreted by SCC-12F2 cells can be accounted for largely or entirely by IL-la, while the activity produced by SCC-12B2 includes IL-la and another unknown factor(s). The BRSA produced by EC-GI-10, BEN, SCC-4, and Epy-1 cells includes both IL-la and PTHrP. We conclude that IL-la may be a more prevalent and biologically significant component of the BRSA produced by SCCs than previously recognized. (Endocrinology127: 3061–3069, 1990)