Journal of Clinical Endocrinology & Metabolism, Vol 67, 592-601, Copyright © 1988 by Endocrine Society
Production of interleukin-1 alpha and a parathyroid hormone-like factor by a squamous cell carcinoma of the esophagus (EC-GI) derived from a patient with hypercalcemia
K Sato, Y Fujii, K Kasono, T Tsushima and K Shizume
Department of Medicine, Tokyo Womens' Medical College, Japan.
To determine the pathogenesis of humoral hypercalcemia associated with
esophageal carcinoma in a 65-yr-old patient, clonal cell lines (EC-GI) were
established from the tumor. The EC-GI cells produced bone- resorbing
activity which eluted from a Sephadex G-75 column in a broad peak, with an
apparent mol wt of 10,000-50,000. In addition to PTH-like factor(s), the
EC-GI cells produced a factor with thymocyte proliferation-stimulating
activity which had an apparent mol wt of 15,000-20,000. This interleukin-1
(IL-1)-like factor(s) with acidic pI (4.8 and 5.2) exactly coeluted with
the bone-resorbing activity upon DEAE-Sepharose ion exchange
chromatography. Both bone-resorbing and thymocyte proliferation-stimulating
activities were completely inhibited by anti-IL-1 alpha antiserum, but not
by anti-IL-1 beta antiserum. Northern blot hybridization studies revealed
that EC-GI cells produced exclusively mRNA for IL-1 alpha. Furthermore,
fractions containing IL-1-like activity and PTH-like activity
synergistically stimulated bone resorption in vitro, and transplantation of
EC-GI cells into nude mice caused hypercalcemia in vivo. These findings
suggest that IL-1 alpha and PTH-like factor produced by this squamous cell
carcinoma synergistically stimulate bone resorption and are related to
humoral hypercalcemia in tumor-bearing nude mice and in the patient.
