Abstract
Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes. On the other hand, angiogenesis is a critical step in tumor growth and metastasis. However, the relationship of adiponectin with vascular endothelial growth factor-A (VEGF-A) expression and angiogenesis in human chondrosarcoma is mostly unknown. In this study we first demonstrated that the expression of adiponectin was correlated with tumor stage of human chondrosarcoma tissues. In addition, we also found that adiponectin increased VEGF-A expression in human chondrosarcoma cells and subsequently induced migration and tube formation in human endothelial progenitor cells (EPCs). Adiponectin promoted VEGF-A expression through adiponectin receptor (AdipoR), phosphoinositide 3 kinase (PI3K), Akt, mammalian target of rapamycin (mTOR), and hypoxia-inducible factor-1α (HIF)-1α signaling cascades. Knockdown of adiponectin decreased VEGF-A expression and also abolished chondrosarcoma conditional medium-mediated tube formation in EPCs in vitro as well as angiogenesis effects in the chick chorioallantoic membrane and Matrigel plug nude mice model in vivo. Therefore, adiponectin is crucial for tumor angiogenesis and growth, which may represent a novel target for anti-angiogenic therapy in human chondrosarcoma.
Highlights
Chondrosarcoma are derived from the abnormal proliferation cartilage
vascular endothelial growth factor-A (VEGF-A)-promoted angiogenesis is a critical step in metastasis of chondrosarcoma [8]
The high level of adiponectin expression correlated strongly with VEGF-A expression and tumor stage (Figure 1C). These results suggest that adiponectin and VEGF-A expression correlates with tumor stage in patients with chondrosarcoma
Summary
Chondrosarcoma are derived from the abnormal proliferation cartilage. Occur at between 10 to 80 years male, and the tumor generally appears on scapula, sternum, ribs, or pelvis [1, 2]. Surgical resection remains the primary mode of therapy for chondrosarcoma. It have been reported that chondrosarcoma can metastasize to other organs, such as lung and liver [3]. When it occurrence of distant metastasis, the patient have a poor prognosis. Until now www.impactjournals.com/oncotarget still lacks an effective adjuvant therapy, the development of novel molecular mechanisms is very important for chondrosarcoma metastasis [4, 5]
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