The prognosis of osteosarcoma with pulmonary metastases is dismal, especially for patients who have primary pulmonary metastases, more than three pulmonary metastatic nodules or involvement of more than one lobe. Factors such as older age, larger tumor volume and elevated LDH may reflect high metastatic rate.

III, therapeutic study.

Osteosarcoma (OS) was a malignant tumor occurring with unknown etiology that made prevention and early diagnosis difficult. Mesenchymal stem cells (MSCs), which were found in bone marrow, were claimed to be a possible origin of OS but with little direct evidence. We aimed to characterize OS cells transformed from human MSCs (hMSCs) and identify their association with human primary OS cells and patient survival. Genetic modification with p53 or retinoblastoma (Rb) knockdown and c‐Myc or Ras overexpression was applied for hMSC transformation. Transformed cells were assayed for proliferation, differentiation, tumorigenecity, and gene expression profile. Only the combination of Rb knockdown and c‐Myc overexpression successfully transformed hMSCs derived from four individual donors, with increasing cell proliferation, decreasing cell senescence rate, and increasing ability to form colonies and spheres in serum‐free medium. These transformed cells lost the expression of certain surface markers, increased in osteogenic potential, and decreased in adipogenic potential. After injection in immunodeficient mice, these cells formed OS‐like tumors, as evidenced by radiographic analyses and immunohistochemistry of various OS markers. Microarray with cluster analysis revealed that these transformed cells have gene profiles more similar to patient‐derived primary OS cells than their normal MSC counterparts. Most importantly, comparison of OS patient tumor samples revealed that a combination of Rb loss and c‐Myc overexpression correlated with a decrease in patient survival. This study successfully transformed human MSCs to OS‐like cells by Rb knockdown and c‐Myc overexpression that may be a useful platform for further investigation of preventive and target therapy for human OS. Stem Cells Translational Medicine 2017;6:512–526

Hemicortical resection for high-grade osteosarcomas located eccentrically in the long bones may be a reliable technique leading to good joint function by preserving surrounding healthy tissues. The functional outcome was encouraging, although long-term follow-up is mandatory to validate. With the advancement of chemotherapy and radiographic three-dimensional imaging, the safe margin in wide excision of high-grade osteosarcoma may be narrowed down in light of joint surface preservation.