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.
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.
Sato
K
K
Department of Medicine, Tokyo Womens' Medical College, Japan.
Fujii
Y
Y
Kasono
K
K
Tsushima
T
T
Shizume
K
K
D000368:Aged; D000818:Animals; D001862:Bone Resorption / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000378:metabolism*; D002845:Chromatography; D004247:DNA / Q000032:analysis; D004938:Esophageal Neoplasms / Q000150:complications / Q000378:metabolism*; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis*; D007525:Isoelectric Focusing; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010281:Parathyroid Hormone / Q000096:biosynthesis*
D007375:Interleukin-1; D010281:Parathyroid Hormone; D004247:DNA; D007213:Indomethacin