Production of interleukin 1 alpha-like factor and colony-stimulating factor by a squamous cell carcinoma of the thyroid (T3M-5) derived from a patient with hypercalcemia and leukocytosis.
In order to elucidate the pathogenesis of humoral hypercalcemia and leukocytosis in a 71-year-old patient with squamous cell carcinoma of the thyroid, bone-resorbing activity (BRA) and colony-stimulating activity in the conditioned medium of T3M-5 cells, a clonal cell line established from the tumor, were studied. Gel chromatography of the concentrated conditioned medium revealed respective single peaks of colony-stimulating activity (Mr approximately 27,000) and BRA (Mr 15,000-20,000). BRA did not elicit parathyroid-hormone-like activity but greatly enhanced phytohemagglutinin-induced thymocyte proliferation. This interleukin 1 (IL-1)-like activity exactly coeluted with BRA upon gel chromatography, DEAE-Sepharose ion-exchange chromatography, and isoelectric focusing (pI, 4.7-5.2). BRA was partially inhibited by indomethacin and hydrocortisone, and completely inhibited by anti-IL-1 alpha antiserum, whereas anti-IL-1 beta antiserum had no effect. Furthermore, transplantation of T3M-5 cells into nude mice caused marked hypercalcemia as well as leukocytosis. These findings suggested that excessive production of colony-stimulating factor and IL-1 alpha-like factor by the squamous cell carcinoma was responsible for leukocytosis and hypercalcemia, respectively, in the tumor-bearing nude mice and in the patient. Since several similar cases have been reported in Japan, the syndrome of leukocytosis and hypercalcemia associated with certain solid tumors may constitute a new paraneoplastic syndrome.
D000368:Aged; D001862:Bone Resorption / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000378:metabolism*; D002852:Chromatography, Ion Exchange; D003115:Colony-Stimulating Factors / Q000096:biosynthesis*; D015232:Dinoprostone; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D006934:Hypercalcemia / Q000150:complications*; D007106:Immune Sera; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis*; D007525:Isoelectric Focusing; D007964:Leukocytosis / Q000150:complications*; D008970:Molecular Weight; D010281:Parathyroid Hormone / Q000494:pharmacology; D011458:Prostaglandins E / Q000096:biosynthesis; D013964:Thyroid Neoplasms / Q000150:complications / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism*
D003115:Colony-Stimulating Factors; D007106:Immune Sera; D007375:Interleukin-1; D010281:Parathyroid Hormone; D011458:Prostaglandins E; D015232:Dinoprostone; D006854:Hydrocortisone; D007213:Indomethacin