Back to Search
Start Over
HTLV-1 Tax transgenic mice develop spontaneous osteolytic bone metastases prevented by osteoclast inhibition
- Publication Year :
- 2005
- Publisher :
- © 2005 by The American Society of Hematology, 2005.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....ede4b2ec1e340cfb6e5f2b56c0ea951c