A NOVEL SPONTANEOUS METASTASIS MODEL OF HUMAN OSTEOSARCOMA DEVELOPED USING ORTHOTOPIC TRANSPLANTATION OF INTACT TUMOR-TISSUE INTO TIBIA OF NUDE-MICE

Evaluation of potential new treatment strategies requires adequate exp erimental tumor models which resemble the clinical situation as closel y as possible, The purpose of the present study was to establish a new human osteosarcoma spontaneous metastasis model using orthotopic tran splantation of histologically intact tumor tissue into the tibia of nu de mice, Intact tumor pieces, obtained from the 32nd serial passage of subcutaneously growing human osteosarcoma xenografts, were implanted into the proximal tibia in 31 nude mice, Animals were sacrificed and a utopsied 2, 4, 6, and 8 weeks after transplantation and examined macro scopically and microscopically for local tumor growth and metastases, All mice developed local intratibial bone tumors that were radiographi cally and histologically similar to primary human osteosarcoma, Lung m etastases were observed in all mice, local and distant lymph node meta stases in 15 (48%), and liver metastases in 6 (19%) mice, The microsco pic appearance of the metastases was similar to that observed in the d onor patient's tumor, corresponding subcutaneous xenografts and orthot opically transplanted intratibial tumors, This spontaneous metastasis model of human osteosarcoma in nude mice may resemble a clinical situa tion and could thus be useful for studies on local tumor growth, metas tasis formation and therapy.