Expression of human transforming growth factor α by chinese hamster ovarian tumors in nude mice causes hypercalcemia and increased osteoclastic bone resorption
| Autor: | M.B. Kester, A. J P Yates, R. Walker, G. Favarato, Lynda F. Bonewald, C. Marcelli, Gregory R. Mundy, Brendan F. Boyce, Thomas B. Aufdemorte, B.C. Langton |
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| Rok vydání: | 2009 |
| Předmět: |
Male
TGF alpha medicine.medical_specialty Endocrinology Diabetes and Metabolism Mice Nude CHO Cells Biology Transfection Bone and Bones Chinese hamster Bone resorption Mice Cricetulus Osteoclast Cricetinae Internal medicine medicine Animals Orthopedics and Sports Medicine Bone Resorption Ovarian Neoplasms Calcium metabolism Mice Inbred BALB C Chinese hamster ovary cell Transforming Growth Factor alpha biology.organism_classification Resorption medicine.anatomical_structure Endocrinology Hypercalcemia Female Cell Division Neoplasm Transplantation Transforming growth factor |
| Zdroj: | Journal of Bone and Mineral Research. 7:847-853 |
| ISSN: | 0884-0431 |
| DOI: | 10.1002/jbmr.5650070715 |
| Popis: | Transforming growth factor alpha (TGF-alpha) 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-alpha can cause hypercalcemia in vivo, we used Chinese hamster ovarian (CHO) cells transfected with the human TGF-alpha gene (TCHO), which stably express and secrete TGF-alpha. 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-alpha 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-alpha is a mediator of hypercalcemia and increased osteoclastic bone resorption in tumors that produce it in sufficient quantity. |
| Databáze: | OpenAIRE |
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