Series subcutaneous transplantation of human glioma cells led to transformation of fibrosarcoma in green fluorescence protein nude mice

Objective To investigate the possibilities of fibrosarcoma transformation in long term serial transplantation of human glioma cells subcutaneously in nude mice with whole body green fluorescence expression. Methods Firstly, 1×106 human brain glioma stem cells SU3 were seeded in NC-C57BL6J-enhanced green fluorescent protein nude mice subcutaneously, and tumors were harvested and cut into pieces (1 mm3/piece) and passaged in vivo continuously; after formation of transplanted tumors, tumor proliferation was observed; histological changes (cells with green fluorescence) were observed under fluorescence microscope; HE staining was performed on the rumor tissues; immunohistochemical staining was used to detect the expressions of hypoxia-inducible factorα(HIF-α), tumor necrosis factor α (TNF-α) and fibroblast activated protein (FAP). Results During the first three generations of transplanted tumors, tumorigenic rate was 100%, but the individual difference of tumor size was obvious; however, tumor size differences decreased when being passaged in vivo after four to eight generations. Tumorigenicity rate was 100% in EGFP nude mice. EGFP positive cells of original host stromal cell ratio during continuous passages in vivo increased gradually. HE staining indicated tumor tissue necrosis and bleeding, abundant blood vessel, large nucleus, deep dyed and abnormal shaped cells, and invasive growth to the muscle gap; immunohistochemical staining showed that the TNF+ and HIF-α+ cells widely distributed at the transplanted tumors of different generations, and no GFAP+ cells were noted; 90% cells had FAP positive expression; fibrosarcomas could be verified. Conclusion Nude mice transplanted tumors originated from human brain glioma stem cells could turn into fibrosarcoma after long term inter-mice passage, which suggests that tumor cells in the host tissue remodeling via parasitic processes can induce malignant transformation of fibrous stroma cells. Key words: Human glioma; Fluorescence nude mouse; Tumor transplantation; Malignant transformation of mesenchymal cell