Paraneoplastic 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.

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 interleukin 1-like activity but potent parathyroid hormone-like activity, which comigrated with BRA. Northern blot hydridization 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.

• Authors: K Sato, Y Fujii, T Kakiuchi, K Kasono, H Imamura, Y Kondo, H Mano, T Okabe, S Asano, F Takaku
• Journal: Cancer research (Cancer Res) Vol. 49 Issue 17 Pg. 4740-6 (Sep 01 1989) ISSN: 0008-5472 [Print] United States
• PMID: 2474371 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biological Factors
• Colony-Stimulating Factors
• Cytokines
• Interleukin-1
• Neoplasm Proteins
• PTHLH protein, human
• Parathyroid Hormone-Related Protein
• RNA, Messenger
• bone resorption factor
• Granulocyte Colony-Stimulating Factor

Topics

• Animals
• Biological Factors (biosynthesis)
• Blotting, Northern
• Carcinoma, Squamous Cell (complications, metabolism)
• Colony-Stimulating Factors (biosynthesis)
• Cytokines
• Granulocyte Colony-Stimulating Factor
• Humans
• Hypercalcemia (etiology)
• Interleukin-1 (biosynthesis)
• Leukocytosis (etiology)
• Male
• Mice
• Mice, Inbred ICR
• Neoplasm Proteins (biosynthesis)
• Paraneoplastic Syndromes (etiology)
• Parathyroid Hormone-Related Protein
• RNA, Messenger (analysis)
• Tumor Cells, Cultured