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Expression of human transforming growth factor α by chinese hamster ovarian tumors in nude mice causes hypercalcemia and increased osteoclastic bone resorption
Author(s) -
Yates A.J.,
Boyce B.F.,
Favarato G.,
Aufdemorte T.B.,
Marcelli C.,
Kester M.B.,
Walker R.,
Langton B.C.,
Bonewald L.F.,
Mundy G.R.
Publication year - 1992
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650070715
Subject(s) - bone resorption , endocrinology , medicine , osteoclast , transforming growth factor , resorption , bone marrow , hamster , bone remodeling , growth factor , in vivo , chemistry , cancer research , biology , receptor , microbiology and biotechnology
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 (Ca 2+ ) 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 Ca 2+ , 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.