Squamous cell carcinomas often produce more than a single bone resorption-stimulating factor: Role of interleukin-1α

R. A. Nowak, N. E. Morrison, D. L. Goad, E. V. Gaffney, A. H. Tashjian

Research output: Contribution to journalArticlepeer-review


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-1α. 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-(1-141), the other recognizing both PTHrP-(1-40) and PTHrP-(1-141)] completely inhibited the cAMP-stimulating activity. Using specific enzyme-linked immunosorbent assays for IL-1α and IL-1β, IL-1α was measured in CM of the SCC-4, SCC-12B2, SCC-12F2, and Epy1 cell lines. IL-1β 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-1α, while the activity produced by SCC-12B2 includes IL-1α and another unknown factor(s). The BRSA produced by EC-GI-10, BEN, SCC-4, and Epy-1 cells includes both IL-1α and PTHrP. We conclude that IL-1α may be a more prevalent and biologically significant component of the BRSA produced by SCCs than previously recognized.

Original languageEnglish (US)
Pages (from-to)3061-3069
Number of pages9
Issue number6
StatePublished - Dec 1990
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology


Dive into the research topics of 'Squamous cell carcinomas often produce more than a single bone resorption-stimulating factor: Role of interleukin-1α'. Together they form a unique fingerprint.

Cite this