Production of bone-resorbing activity and colony-stimulating activity in vivo and in vitro by a human squamous cell carcinoma associated with hypercalcemia and leukocytosis

K Sato, H Mimura, D C Han, T Kakiuchi, Y Ueyama, H Ohkawa, T Okabe, Y Kondo, N Ohsawa, T Tsushima, K Sato, H Mimura, D C Han, T Kakiuchi, Y Ueyama, H Ohkawa, T Okabe, Y Kondo, N Ohsawa, T Tsushima

Abstract

A squamous cell carcinoma of 33-yr-old patient who developed marked leukocytosis and hypercalcemia was transplanted into nude mice in which more marked leukocytosis and hypercalcemia also developed. This tumor (LJC-1-JCK) produced a colony-stimulating factor (CSF) and formed a cyst in the tumor from which a CSF-producing cell line (T3M-1) was established. The CSF causes predominantly formation of granulocytic colonies in addition to macrophage colonies. Bone-resorbing activity (BRA) was detected in the cystic fluid and was eluted as two separate peaks with proteins of an apparent molecular weight of 30,000-50,000 and 10,000-20,000. Colony-stimulating activity (CSA) was eluted at an apparent 30,000 mol wt. The conditioned medium of the T3M-1 cells also contained a BRA with an apparent 14,000 mol wt, whereas CSA eluted at an apparent 30,000 mol wt. PTH, epidermal growth factor, transforming growth factor-alpha, prostaglandin Es, and vitamin D could not account for the powerful BRA. In contrast to CSA, BRA was not inactivated by trypsin and more stable at 70 degrees C. When T3M-1 cells were transplanted into nude mice, marked hypercalcemia developed in addition to granulocytosis. Our findings suggest that the tumor produces and secretes a powerful BRA in vivo and in vitro, which is different from CSA in terms of molecular weight, heat stability, and trypsin treatment. We speculate that the synergistic action of CSF that stimulates macrophage colony formation and recruits osteoclast precursors, and BRA, which stimulates mononuclear phagocytes and/or osteoclasts were responsible for a marked increase in osteoclastic bone resorption and humoral hypercalcemia in the patient.

References

    1. J Biol Chem. 1971 Nov 25;246(22):6782-5
    1. J Clin Endocrinol Metab. 1982 Aug;55(2):219-27
    1. J Clin Invest. 1975 Aug;56(2):408-13
    1. Proc Natl Acad Sci U S A. 1975 Jul;72(7):2635-9
    1. J Biol Chem. 1977 Jun 25;252(12):4305-12
    1. Immunobiology. 1982 Apr;161(3-4):193-203
    1. Blood. 1983 Mar;61(3):600-3
    1. J Clin Invest. 1983 Mar;71(3):769-74
    1. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1454-8
    1. Cancer Res. 1983 May;43(5):2368-74
    1. Proc Soc Exp Biol Med. 1983 Apr;172(4):424-9
    1. J Biol Chem. 1983 Jul 25;258(14):9017-23
    1. J Immunol. 1983 Jul;131(1):109-14
    1. N Engl J Med. 1983 Aug 11;309(6):325-30
    1. Science. 1983 Sep 23;221(4617):1292-4
    1. J Clin Invest. 1983 Oct;72(4):1511-5
    1. Nature. 1983 Nov 24-30;306(5941):378-80
    1. N Engl J Med. 1984 Jun 28;310(26):1718-27
    1. J Immunol. 1985 Feb;134(2):772-8
    1. Science. 1985 May 24;228(4702):1007-9
    1. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4535-8
    1. Cancer. 1985 Aug 15;56(4):782-8
    1. J Clin Invest. 1965 Jan;44:103-16
    1. Cancer Res. 1978 Nov;38(11 Pt 1):3910-7
    1. Calcif Tissue Res. 1978 Aug 18;25(3):233-40
    1. J Lab Clin Med. 1978 Nov;92(5):772-8
    1. Biochem Biophys Res Commun. 1978 Dec 14;85(3):966-75
    1. Cancer. 1979 Feb;43(2):605-10
    1. J Exp Med. 1979 Aug 1;150(2):338-50
    1. Biochem J. 1979 Jul 15;182(1):55-69
    1. Nature. 1980 Feb 14;283(5748):669-70
    1. Gan. 1979 Dec;70(6):807-10
    1. Endocrinology. 1980 Jul;107(1):270-3
    1. J Immunol. 1980 Sep;125(3):1302-5
    1. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3494-8
    1. J Clin Endocrinol Metab. 1981 Nov;53(5):941-7
    1. Cancer. 1981 Nov 1;48(9):2080-3
    1. J Cell Physiol. 1982 Jan;110(1):43-9
    1. Nihon Jibiinkoka Gakkai Kaiho. 1981 Dec 20;84(12):1554-61
    1. Endocrinology. 1982 Jul;111(1):118-24
    1. J Urol. 1973 Dec;110(6):660-3

Source: PubMed

3
구독하다