Fig. 2: HIF-2α promotes tumor growth and metastatic propensity of chondrosarcoma in xenograft animal models.
From: A system-level approach identifies HIF-2α as a critical regulator of chondrosarcoma progression
a Primary chondrosarcoma tumors formed in tibial intramedullary canal following orthotopic SW1353 xenograft. Images represent one of five experiments, with similar results obtained. BM, bone marrow; B, bone; T, tumor. Scale bars: 300 μm (top panel), 25 μm (middle and bottom panels). b IF images in primary and pulmonary metastatic tumors. T, tumor; B, bone; L, lung (upper panel). The percentage of HIF-2α positive cells among human mitochondria-positive cells (n = 6, primary tumors; 8, lung metastases, lower panel). Scale bars: 25 μm. c, d H&E images illustrating the extent of local invasion of c SW1353 and d JJ012 cells harboring indicated shRNAs into the muscle tissue surrounding the tibia (left panel). Percentage of mice bearing extraosseous outgrowths that originated from the intramedullary region and invaded into the surrounding muscle (n = 6, SW1353; 6, JJ012; right panel). M, muscle; T, tumor; B, bone. Scale bars: 50 μm. e, f Quantitation of Ki-67 positivity in primary tumors established with e SW1353 (n = 4) or f JJ012 (n = 4) cells harboring indicated shRNAs. g, h Metastatic growth of g SW1353 (n = 6) and h JJ012 (n = 6) cells harboring indicated shRNAs (left panel). The percentage of mice bearing lung metastases (middle panel) and the number of metastatic foci (right panel). Scale bars: 50 μm. i, j Pulmonary metastasis of orthotopically transplanted SW1353 cells overexpressing eGFP or EPAS1 (n = 6, eGFP#1; 5, eGFP#2; 6, EPAS1#1; 4, EPAS1#2). i The percentage of mice bearing lung metastases and j the number of metastatic foci in the indicated groups. k Growth of JJ012 tumor harboring control or EPAS1 shRNAs in the subcutaneous xenograft model (n = 5). The tumor volume at the indicated days after transplantation. l Gross images (left panel) and the weight (n = 5, right panel) of excised chondrosarcoma tumors at the end of the experiment. Data represent mean ± SEM. P-values are from two-tailed t test (b, e–h, l), one-way ANOVA (j), or two-way ANOVA (k).
