Ewing's sarcoma of bone tumor cells produces MCSF that stimulates monocyte proliferation in a novel mouse model of Ewing's sarcoma of bone

Abstract

Ewing's sarcoma of bone is a primary childhood malignancy of bone that is treated with X-radiation therapy in combination with surgical excision and chemotherapy. To better study Ewing's sarcoma of bone we developed a novel model of primary Ewing's sarcoma of bone and then treated animals with X-radiation therapy. We identified that uncontrolled tumor resulted in lytic bone destruction while X-radiation therapy decreased lytic bone destruction and increased limb-length asymmetry, a common, crippling complication of X-radiation therapy. Osteoclasts were indentified adjacent to the tumor, however, we were unable to detect RANK-ligand in the Ewing's tumor cells in vitro, which lead us to investigate alternate mechanisms for osteoclast formation. Ewing's sarcoma tumor cells and archival Ewing's sarcoma of bone tumor biopsy samples were shown to express MCSF, which could promote osteoclast formation. Increased monocyte numbers were detected in peripheral blood and spleen in animals with untreated Ewing's sarcoma tumor while monocyte number in animals treated with x-radiation had normal numbers of monocytes. Our data suggest that our Ewing's sarcoma of bone model will be useful in the study Ewing's sarcoma tumor progression in parallel with the effects of chemotherapy and X-radiation therapy.

Identification of Factors Driving Doxorubicin-Resistant Ewing Tumor Cells to Survival

“…Progression and metastasis of ES is a complex biological process that involves bone lytic destruction and tumor cell propagation. It has been demonstrated that ES cells initiate osteolysis on the border between normal and neoplastic tissue via increased immobilization of macrophages, since they have been involved in the destruction of the bone extracellular collagen-containing matrix (ECCM) [ 7 ]. Along with the activation of osteoclast differentiation [ 8 ], ECCM destruction lays a foundation for tumor vascularization in the area of bone resorption and activation of angiogenesis [ 9 ].…”