Cancer Immunology, Immunotherapy

, Volume 39, Issue 3, pp 155–160

Comparative study of inhibitory effects by murine interferon γ and a new bisphosphonate (alendronate) in hypercalcemic, nude mice bearing human tumor (LJC-1-JCK)

  • Masahiro Tohkin
  • Shinji Kakudo
  • Hisashi Kasai
  • Hitoshi Arita
Original Articles Interferon γ, Hypercalcemia, Bisphosphonate, Bone-Resorption, Parathyroid Hormone-Related Protein

DOI: 10.1007/BF01533380

Cite this article as:
Tohkin, M., Kakudo, S., Kasai, H. et al. Cancer Immunol Immunother (1994) 39: 155. doi:10.1007/BF01533380

Abstract

The inhibitory effect of murine interferon γ (muIFNγ) on humoral hypercalcemia in nude mice bearing lower-jaw cancer (LJC-1-JCK), in which parathyroid-hormone(PTH)-related protein is responsible for causing humoral hypercalcemia by activating bone resorption, was examined in comparison with that of a new bisphosphonate, 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (alendronate), muIFNγ was injected into tumor-bearing nude mice for 5 days before the establishment of hypercalcemia. The increase of plasma calcium concentration was delayed and this effect continued for more than 6 days even after the injection was stopped. Alendronate markedly suppressed hypercalcemia in tumor-bearing nude mice but this inhibitory effect continued for less than 6 days. Neither muIFNγ nor alendronate affected the tumor volume or serum PTH-related protein concentration. Injection of muIFNγ into mice for 3 days almost completely abolished the formation of multinucleated osteoclast-like cells from bone marrow cells in vitro, whereas injection of alendronate into mice had no effect. These findings suggested that muIFNγ suppressed the formation of osteoclasts, resulting in the prolonged decrease of plasma calcium concentration in hypercalcemic tumor-bearing nude mice, whereas alendronate is cytotoxic to functionally mature osteoclasts and inhibited osteoclastic bone resorption, resulting in a marked decrease in the plasma calcium concentration in tumor-bearing hypercalcemic nude mice.

Key words

Interferon γ Hypercalcemia Bisphosphonate Bone-resorption Parathyroid hormone-related protein 

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Masahiro Tohkin
    • 1
  • Shinji Kakudo
    • 1
  • Hisashi Kasai
    • 1
  • Hitoshi Arita
    • 1
  1. 1.Shionogi Research LaboratoriesShionogi & Co. Ltd.OsakaJapan

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