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Production of Interleukin-1 and a Parathyroid Hormone-Like Factor by a Squamous Cell Carcinoma of the Esophagus (EC-GI) Derived From a Patient With Hypercalcemia^*

Department of Medicine, Institute of Clinical Endocrinology, Tokyo Womens' Medical College (K.Sa., K.K., T.T., K.Sh.) Kawada-cho 8-1, Japan
the Research Institute of the Foundation for Growth Science in Japan (K.Sa, Y.F., T.T., K.Sh.) Shinjuku-ku, Tokyo, Japan

Address requests for reprints to: Dr. Kanji Sato, Department of Medicine, Tokyo Womens' Medical College, Kawada-cho 8-1, Shinjuku-ku, Tokyo 162, Japan.

To determine the pathogenesis of humoral hypercalcemia associated with esophageal carcinoma in a 65-yrold 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-l)-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-l antiserum, but not by anti-IL-1β antiserum. Northern blot hybridization studies revealed that EC-GI cells produced exclusively mRNA for IL-l. 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 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.

^* Part of this work was presented at the Ninth International Conference on Calcium-Regulating Hormones, Nice, France, October 1986 (Abstract 271), and at the Ninth Annual Meeting of the American Society for Bone and Mineral Research, Indianapolis, IN, June 6–9, 1987 (Abstract 387). This work was supported by a Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture, Japan (61570563 and 62570521), a Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare, Japan (60-29), a research grant from the Foundation for Growth Science in Japan (especially donations from Mrs. Toshiko Sato), and a research grant from Bone-Regulating Peptides from Chugai Pharmaceutical Co. (Tokyo, Japan).

Received February 8, 1988.

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