Resistin enhances angiogenesis in osteosarcoma via the MAPK signaling pathway

Abstract

Over the last two decades, there have been no significant changes in patient outcomes in relation to the treatment of osteosarcoma, an aggressive malignant neoplasm. It is known that vascular endothelial growth factor-A (VEGF-A) plays a crucial role in angiogenesis and in osteosarcoma. Moreover, VEGF-A expression correlates with clinical stages of osteosarcoma. The adipokine resistin exhibits proinflammatory, proangiogenic and metastatic properties, and evidence suggests that resistin may serve as a prognostic biomarker linking obesity and inflammation to cancer. However, whether resistin has a role in osteosarcoma angiogenesis is unclear. This investigation shows that resistin promotes VEGF-A expression in human osteosarcoma cells and activates the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 signaling pathways, while ERK, JNK, and p38 inhibitors or their small interfering RNAs (siRNAs) inhibit resistin-induced VEGF-A expression as well as endothelial progenitor cell (EPC) migration and tube formation. We also found that resistin upregulates VEGF-A expression by enhancing activation of the transcription factor nuclear factor-kappa B (NF-κB). Finally, resistin promotes angiogenesis in the chick chorioallantoic membrane (CAM) model. Resistin appears to be a promising target for human osteosarcoma.

Association between excessive chronic iodine exposure and the occurrence of papillary thyroid carcinoma

“…However, only high levels of iodine were able to upregulate the expression of vascular endothelial growth factor (VEGF)-A in W3 cells (21), MAPK in TPC-1 cells (22), and AKT in TFC (thyroid follicular cells) (23). AKT and MAPK are involved in the PI3K/AKT/mTOR and MAPK signaling pathways, respectively (24,25); both activate downstream VEGF (26,27), which is responsible for angiogenic activation and immune microenvironment disorders in carcinomas (27,28), contributing to proliferation and metastasis (29)(30)(31)(32)(33)(34)(35). It was therefore hypothesized that only high concentrations of iodine can trigger the activation of the PI3K/AKT/mTOR and MAPK pathways and alter VEGF-mediated angiogenesis and immune reactions, thereby promoting the proliferation and metastasis of PTC.…”

High Expression of Both Resistin and Fascin‐1 Predicts a Poor Prognosis in Patients with Colorectal Cancer

“…The adipokine resistin participates in several physiologic and pathologic processes throughout the body, including metabolism, inflammation, autoimmunity, and various cancers, including CRC [3][4][5][6][7][8][9]. Previous research has documented an association between higher levels of circulating resistin and an increased risk for CRC [10].…”

“…In our previous study, we found that epidermal growth factor induced the expression of fascin-1 by activating p44/p42 MAPK (ERK1/2), which subsequently promoted breast cancer cell migration and invasion [17]. Other reports have shown that resistin promotes angiogenesis in osteosarcoma and proliferation of smooth muscle cells through p44/p42 MAPK (ERK1/2) signaling [9,18]. Up until now, there have been no reports documenting an association between resistin and fascin-1.…”

“…Resistin is a cytokine secreted by adipocytes that participates in the body's metabolism, inflammation, and autoimmunity through multiple molecular pathways [3]. While initial research focused on obesity and insulin resistance, resistin was later implicated in the occurrence and progression of various malignant tumors [4][5][6][7][8][9]. Evidence demonstrates that higher levels of circulating resistin increase the risk of developing CRC [10].…”

CXCL13/CXCR5 Interaction Facilitates VCAM-1-Dependent Migration in Human Osteosarcoma

“…However, despite such treatment, only 60–70% of patients without clinically evident metastasis at first diagnosis remain alive after 3 years [ 2 ]. Major challenges that reduce overall survival of patients with osteosarcoma include the development of chemoresistance and progression to lung metastasis [ 3 , 4 , 5 ]. Since the lung is the most frequent organ affected by metastasis in osteosarcoma [ 2 ], the development of therapeutic strategies for delaying or inhibiting lung metastasis progression remains critical for improving patient survival outcomes.…”