Tumors producing human tumor necrosis factor induce hypercalcemia and osteoclastic bone resorption in nude mice

R. A. Johnson, B. F. Boyce, G. R. Mundy, G. David Roodman

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

We used a Chinese hamster ovary cell line that had been transfected with the human tumor necrosis factor (TNF) gene and constitutively produced TNF when transplanted in nude mice to study the effects of continuous production of TNF on calcium homeostasis. Continuous exposure to TNF caused increased osteoclastic bone resorption and humoral hypercalcemia in these animals. The mice bearing TNF-producing tumors were significantly hypercalcuric compared to mice bearing control tumors, but urinary cAMP excretion was unchanged. Mice bearing Chinese hamster ovary cell tumors containing the empty vector did not demonstrate hypercalcemia or increased bone resorption. This model system using transfected cells to continuously produce cytokines in vivo is more analogous to the pathophysiological conditions present in patients than intermittent injections and can produce much longer exposures than infusion pumps. Such model systems should allow a better understanding of the role of factors involved in humoral hypercalcemia.

Original languageEnglish
Pages (from-to)1424-1427
Number of pages4
JournalEndocrinology
Volume124
Issue number3
StatePublished - 1989
Externally publishedYes

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Hypercalcemia
Bone Resorption
Nude Mice
Tumor Necrosis Factor-alpha
Cricetulus
Ovary
Neoplasms
Infusion Pumps
Homeostasis
Cytokines
Calcium
Cell Line
Injections
human TNF protein
Genes

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Tumors producing human tumor necrosis factor induce hypercalcemia and osteoclastic bone resorption in nude mice. / Johnson, R. A.; Boyce, B. F.; Mundy, G. R.; Roodman, G. David.

In: Endocrinology, Vol. 124, No. 3, 1989, p. 1424-1427.

Research output: Contribution to journalArticle

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