PARA-NEOPLASTIC SYNDROME OF HYPERCALCEMIA AND LEUKOCYTOSIS CAUSED BY SQUAMOUS CARCINOMA-CELLS (T3M-1) PRODUCING PARATHYROID HORMONE-RELATED PROTEIN, INTERLEUKIN-1-ALPHA, AND GRANULOCYTE COLONY-STIMULATING FACTOR

  • 1 September 1989
    • journal article
    • research article
    • Vol. 49  (17) , 4740-4746
Abstract
Previously we reported that a clonal squamous cell carcinoma cell line (T3M-1) derived from a lower jaw cancer of a patient with marked leukocytosis and hypercalcemia produced factors containing a potent bone-resorbing activity (BRA) (Mr 15,000-20,000) and a colony-stimulating activity. To elucidate the pathogenesis of this humoral hypercalcemia, BRA and colony-stimulating activity in both the conditioned medium and cells were characterized. The conditioned medium, when eluted at neutral pH, contained colony-stimulating activity and thymocyte proliferation-stimulating activity, the latter of which comigrated with BRA. Upon elution with acetic acid (pH 2.0), the conditioned medium contained no interluekin 1-like activity but potent parathyroid hormone-like activity, which comigrated with BRA. Northern blot hybridization analysis revealed that T3M-1 cells produced constitutively mRNA for parathyroid hormone-related protein and granulocyte colony-stimulating factor. Furthermore, primer extension analysis revealed that the cells also produced mRNA for interleukin 1.alpha.(IL-1.alpha.). Since parathyroid hormone-related protein and IL-1.alpha. (osteoclast-activating factor) synergistically increase the concentration of serum calcium, and since IL-1.alpha. (hemopoietin 1) potentiates granulocyte colony-stimulating factor-induced granulocytopoiesis, we speculate that parathyroid hormone-related protein, granulocyte colony-stimulating factor, and IL-1.alpha. are synergistically involved in a paraneoplastic syndrome of hypercalcemia and leukocytosis, at least in some patients with solid tumors.