WISP-1 positively regulates angiogenesis by controlling VEGF-A expression in human osteosarcoma

Abstract

In recent years, much research has focused on the role of angiogenesis in osteosarcoma, which occurs predominantly in adolescents and young adults. The vascular endothelial growth factor-A (VEGF-A) pathway is the key regulator of angiogenesis and in osteosarcoma. VEGF-A expression has been recognized as a prognostic marker in angiogenesis. Aberrant WNT1-inducible signaling pathway protein-1 (WISP-1) expression is associated with various cancers. However, the function of WISP-1 in osteosarcoma angiogenesis is poorly understood. We demonstrate a positive correlation between WISP-1 and VEGF-A expression in human osteosarcoma. Moreover, we show that WISP-1 promotes VEGF-A expression in human osteosarcoma cells, subsequently inducing human endothelial progenitor cell (EPC) migration and tube formation. The focal adhesion kinase (FAK), Jun amino-terminal kinase (JNK), and hypoxia-inducible factor (HIF)-1α signaling pathways were activated after WISP-1 stimulation, while FAK, JNK, and HIF-1α inhibitors or small interfering RNA (siRNA) abolished WISP-1-induced VEGF-A expression and angiogenesis. In vitro and in vivo studies revealed down-regulation of microRNA-381 (miR-381) in WISP-1-induced VEGF-A expression and angiogenesis. Our findings reveal that WISP-1 enhances VEGF-A expression and angiogenesis through the FAK/JNK/HIF-1α signaling pathways, as well as via down-regulation of miR-381 expression. WISP-1 may be a promising target in osteosarcoma angiogenesis.

Human Leukocyte Antigen F Locus Adjacent Transcript 10 Overexpression Disturbs WISP1 Protein and mRNA Expression to Promote Hepatocellular Carcinoma Progression

“…However, the expression and function of WISP1 in various tumors are reported differently. Some studies have reported that WISP1 is highly expressed in some tumors and functions as an oncogene . However, other studies have also demonstrated that WISP1 has low expression in tumor and plays the role of a tumor suppressor gene.…”

“…Some studies have reported that WISP1 is highly expressed in some tumors and functions as an oncogene. (26)(27)(28) However, other studies have also demonstrated that WISP1 has low expression in tumor and plays the role of a tumor suppressor gene. Patients with low expression of WISP1 had a poor prognosis.…”

The role of CCN4/WISP-1 in the cancerous phenotype

“…In a subsequent study published in 2017, the same group examined the role of CCN4 in angiogenesis in osteosar-coma 48. They found that exogenous CCN4 increased VEGF-A expression at the transcriptional level in an osteosarcoma cell line, MG-63.…”

“…This work was from the same group that had studied CCN4 in osteosarcoma 47,48. With respect to human chondrosarcoma, the investigators found that CCN4 expression was elevated in chondrosarcoma tissues as compared to normal cartilage.…”

Untangling the response of bone tumor cells and bone forming cells to matrix stiffness and adhesion ligand density by means of hydrogels

“…Vinculin is an important molecule that stabilizes FAs and modulates force transmission[43]. Studies have reported that stress stimulates the combined expression of vinculin and paxillin, thereby activating FAK[18, 19, 44] to eventually promote the expression of tumor malignancy markers, such as MMP2, MMP9 and VEGF[45]. During mechanotransduction, the Wnt-independent activation of β-catenin is also initiated by FAK upregulation[46] to increase MMP2 and MMP9 activity, thereby contributing to tumorigenesis[47].…”