HTLV-1 Tax transgenic mice develop spontaneous osteolytic bone metastases prevented by osteoclast inhibition
| العنوان: | HTLV-1 Tax transgenic mice develop spontaneous osteolytic bone metastases prevented by osteoclast inhibition |
|---|---|
| المؤلفون: | Katherine N. Weilbaecher, Lee Ratner, Angela C. Hirbe, Ling Gao, John C. S. Harding, Hongju Deng, Haibo Zhao |
| بيانات النشر: | © 2005 by The American Society of Hematology, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | musculoskeletal diseases, Bone disease, Large granular lymphocytic leukemia, Immunology, Organophosphonates, Osteoclasts, Bone Neoplasms, Mice, Transgenic, Biochemistry, Metastasis, Mice, Osteoprotegerin, Osteoclast, Bone Density, Medicine, Animals, Lymphocytes, Cells, Cultured, Human T-lymphotropic virus 1, Lymphokines, Neoplasia, business.industry, Interleukin-6, Bone metastasis, Cell Biology, Hematology, Gene Products, tax, medicine.disease, Lymphoma, Leukemia, medicine.anatomical_structure, Gene Expression Regulation, Hypercalcemia, business |
| الوصف: | One in 20 carriers of human T-cell leukemia virus type 1 (HTLV-1) will develop adult T-cell leukemia/lymphoma (ATL), a disease frequently associated with hypercalcemia, bone destruction, and a fatal course refractory to current therapies. Overexpression of the HTLV-1–encoded Tax oncoprotein under the human granzyme B promoter causes large granular lymphocytic leukemia/lymphomas in mice. We found that Tax+ mice spontaneously developed hypercalcemia, high-frequency osteolytic bone metastases, and enhanced osteoclast activity. We evaluated Tax tumors for the production of osteoclast-activating factors. Purification of Tax+ tumor cells and nonmalignant tumor-infiltrating lymphocytes demonstrated that each of these populations expressed transcripts for distinct osteoclast-activating factors. We then evaluated the effect of osteoclast inhibition on tumor formation. Mice doubly transgenic for Tax and the osteoclast inhibitory factor, osteoprotegerin, were protected from osteolytic bone disease and developed fewer soft-tissue tumors. Likewise, osteoclast inhibition with bone-targeted zoledronic acid protected Tax+ mice from bone and soft-tissue tumors and prolonged survival. Tax+ mice represent the first animal model of high-penetrance spontaneous osteolytic bone metastasis and underscore the critical role of nonmalignant host cells recruited by tumor cells in the process of cancer progression and metastasis. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ede4b2ec1e340cfb6e5f2b56c0ea951cTest https://europepmc.org/articles/PMC1895233Test/ |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ede4b2ec1e340cfb6e5f2b56c0ea951c |
| قاعدة البيانات: | OpenAIRE |
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