Adaptive Fibrogenic Reprogramming of Osteosarcoma Stem Cells Promotes Metastatic Growth.

It is well established that fibrotic remodeling of the tumor microenvironment favors tumorigenesis, but whether fibrosis underlies malignant progression in other ways is unclear. Here, we report that adaptive myofibroblastic reprogramming of osteosarcoma stem cells (OSCs) results in a critical advantage when establishing lung macro-metastases and spheroid growth but does not affect the growth of primary lesions or monolayer cultures. FGFR2 signaling in OSCs initiates fibrosis, whereas the resultant fibronectin (FN) auto-deposition sustains fibrogenic reprogramming and OSC growth, resembling the process employed by non-malignant myofibroblasts to cause tissue fibrosis. Furthermore, we provide evidence that nintedanib targets the pan FGFR-FN axis to disrupt lung metastasis without affecting the bone lesion growth of OSCs. Thus, myofibroblastic reprogramming of human OSCs in the lungs might represent a druggable trait for treating a deadly metastatic complication.

Surgical treatment of Ideberg type III glenoid fractures with associated superior shoulder suspensory complex injury.

Ideberg type III glenoid fractures with associated superior shoulder suspensory complex (SSSC) injuries are rare, and related treatments have not been reported in the literature. The purpose of this study was to evaluate the clinical outcomes of such injuries treated with open reduction and internal fixation (ORIF). Between July 2007 and April 2012, ten patients with Ideberg type III glenoid fractures were surgically treated using ORIF with 2 cannulated screws or a screw combined with a metacarpal plate through an anterior approach. Patients with associated SSSC injuries underwent ORIF with K-wires or plates. Information was available for 9 patients with a mean follow-up of 24.1±18.2 months. Mean bone-healing time was 8.4±2.2 weeks. At last follow-up, mean forward flexion of the operative shoulder was 157.8°±7.5°, mean external rotation was 62.9°±7.9°, and mean internal rotation was thoracic level T6±0.8. Mean Constant score was 84.1±3.7 points, which was a mean of 92.7%±3.4% of that seen in the contralateral shoulder. Mean UCLA score and Disabilities of the Arm, Shoulder and Hand score were 33.6±1.7 and 16.6±7.7, respectively. The results show that Ideberg type III glenoid fractures with associated SSSC injuries can be successfully treated using ORIF through an anterior approach. Glenoid fractures and SCCC injuries should be treated simultaneously.