Two squamous cell carcinomas not associated with humoral hypercalcemia produce a potent bone resorption-stimulating factor which is interleukin-1α

R. M. Fried, E. F. Voelkel, R. H. Rice, L. Levine, E. V. Gaffney, A. H. Tashjian

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Conditioned medium (CM) from two squamous cell carcinoma cell lines, SCC-9 and SCC-13, stimulated bone resorption in neonatal mouse calvariae in organ culture. Enhanced bone resorption induced by CM was associated with an increased production of prostaglandin-E2 (PGE2) by the calvariae. Complete inhibition of stimulated PGE2 synthesis by indomethacin only partially inhibited bone resorption-stimulating activity (BRSA) in the CM. Neither SCC-9 nor SCC-13 CM stimulated cAMP production in rat osteosarcoma cells (ROS 17/2.8). The BRSA in CM was completely inhibited by an antibody to interleukin-1α (IL-1α). Fractionation of SCC-9 CM by gel filtration and HPLC ion exchange chromatography revealed a single peak of BRSA and PGE2 synthesis-stimulating activity at 17-20K (termed SCM(II)). In mouse calvariae, SCM(II) increased medium Ca2+ and PGE2 in a dose-dependent manner at concentrations from 20 ng protein/ml to a maximum of 500 ng protein/ml. Preincubation of SCM(II) with antibody to IL-1α completely inhibited SCM(II)-induced bone resorption. SCM(II) also enhanced thymocyte proliferation with activity that was equivalent to 353 U/ml IL-1. Antibodies to IL-1β and tumor necrosis factor had no effect on SCM(II)-induced bone resorption. Using specific enzyme-linked immunosorbent assays for IL-1α and IL-1β, IL-1α was measured in high concentrations in both crude and partially purified fractions of SCC-9 and SCC-13 CM. In contrast, IL-1β was either undetectable or present in amounts below those that stimulate bone resorption. In addition, SCM(II) did not enhance cAMP production in bone cells. We conclude that the BRSA produced by the two squamous cell carcinoma cell lines SCC-9 and SCC-13 is IL-1α.

Original languageEnglish (US)
Pages (from-to)742-751
Number of pages10
JournalEndocrinology
Volume125
Issue number2
StatePublished - 1989
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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