Back to Search
Start Over
Interferon-γ Targets Cancer Cells and Osteoclasts to Prevent Tumor-associated Bone Loss and Bone Metastases.
- Source :
-
Journal of Biological Chemistry . 2/13/2009, Vol. 284 Issue 7, p4658-4666. 9p. 5 Diagrams. - Publication Year :
- 2009
-
Abstract
- Interferon-γ (IFN-γ) has been shown to enhance anti-tumor immunity and inhibit the formation of bone-resorbing osteoclasts. We evaluated the role of IFN-γ in bone metastases, tumor-associated bone destruction, and hypercalcemia in human T cell lympho-trophic virus type 1-Tax transgenic mice. Compared with Tax+IFN-γ+/+ mice, Tax+IFN-γ-/- mice developed increased osteolytic bone lesions and soft tissue tumors, as well as increased osteoclast formation and activity. In vivo administration of IFN-γ to tumor-bearing Tax+IFN-γ-/- mice prevented new tumor development and resulted in decreased bromodeoxyuridine uptake by established tumors. In vitro, IFN-γ directly decreased the viability of Tax+ tumor cells through inhibition of proliferation, suppression of ERK phosphorylation, and induction of apoptosis and caspase 3 cleavage. IFN-γ also inhibited macrophage colony- stimulating factor-mediated proliferation and survival of osteoclast progenitors in vitro. Administration of IFN-γ to C57BL/6 mice decreased Tax+ tumor growth and prevented tumor-associated bone loss and hypercalcemia. In contrast, IFN-γ treatment failed to protect IFN-γRF-/- mice from Tax+ tumor-induced skeletal complications, despite decreasing tumor growth. These data demonstrate that IFN-γ suppressed tumor-induced bone loss and hypercalcemia in Tax+ mice by inhibiting both Tax+ tumor cell growth and host-induced osteolysis. These data suggest a protective role for IFN-γ in patients with bone metastases and hypercalcemia of malignancy. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 284
- Issue :
- 7
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 37151805
- Full Text :
- https://doi.org/10.1074/jbc.M804812200