Expression of human transforming growth factor α by chinese hamster ovarian tumors in nude mice causes hypercalcemia and increased osteoclastic bone resorption

A. J. Yates, B. F. Boyce, G. Favarato, T. B. Aufdemorte, C. Marcelli, M. B. Kester, R. Walker, B. C. Langton, L. F. Bonewald, G. R. Mundy

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Transforming growth factor α (TGF‐α) is a polypeptide regulator of cell growth produced by many malignant tumors. It stimulates osteoclastic resorption in bone organ culture and osteoclast‐like cell formation in marrow culture. To determine whether tumor production of TGF‐α can cause hypercalcemia in vivo, we used Chinese hamster ovarian (CHO) cells transfected with the human TGF‐α gene (TCHO), which stably express and secrete TGF‐α. We used nontransfected CHO cells as controls (CCHO). TCHO and CCHO were inoculated intramuscularly into one hindlimb of nude mice and grew as local solid tumors. After 4 weeks of TCHO tumor growth, plasma ionized calcium (Ca2+) increased to reach 1.48 ± 0.03 mM (mean ± SEM), whereas mice bearing similarly sized CCHO tumors and non‐tumor‐bearing mice (NTB) remained normocalcemic (normal range for Ca2+, 1.15–1.30 mM). Plasma TGF‐α was undetectable by an ELIFA assay in all NTB mice, was markedly increased in all TCHO mice (5.75 ± 0.78 ng/ml), and was slightly increased in CCHO mice (0.50 ± 0.22 ng/ml). Quantitative bone histomorphometry showed a prominent increase in osteoclastic bone resorption in TCHO mice. These data suggest that TGF‐α is a mediator of hypercalcemia and increased osteoclastic bone resorption in tumors that produce it in sufficient quantity.

Original languageEnglish (US)
Pages (from-to)847-853
Number of pages7
JournalJournal of Bone and Mineral Research
Volume7
Issue number7
DOIs
StatePublished - Jul 1992
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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