CCL3 promotes angiogenesis by dysregulation of miR-374b/ VEGF-A axis in human osteosarcoma cells

Abstract

Osteosarcoma is the most frequent bone tumor, characterized by a high metastatic potential. However, the crosstalk between chemokine (C-C motif) ligand 3 (CCL3), which facilitates tumor progression and metastasis. Vascular endothelial growth factor-A (VEGF-A), an angiogenesis inducer and a highly specific mitogen for endothelial cells, has not been well explored in human osteosarcoma. Here we demonstrate the correlation of CCL3 and VEGF-A expressions, quantified by immunohistochemistry, with the tumor stage of human osteosarcoma tissues. Furthermore, CCL3 promotes VEGF-A expression in human osteosarcoma cells that subsequently induces human endothelial progenitor cell (EPC) migration and tube formation. Phosphorylation of JNK, ERK, and p38 was found after CCL3 stimulation. In addition, JNK, ERK, and p38 inhibitors also abolished CCL3-induced VEGF-A expression and angiogenesis. We noted that CCL3 reduces the expression of miR-374b and miR-374b mimic by reversing CCL3-promoted VEGF-A expression and angiogenesis in vitro and in vivo. This study shows that CCL3 promotes VEGF-A expression and angiogenesis in human osteosarcoma cells by down-regulating miR-374b expression via JNK, ERK, and p38 signaling pathways. Thus, CCL3 may be a new molecular therapeutic target in osteosarcoma angiogenesis and metastasis.

MicroRNA‐374b inhibits cervical cancer cell proliferation and induces apoptosis through the p38/ERK signaling pathway by binding to JAM‐2

“…In comparison to the blank and NC groups, expression of miR‐374b and mRNA levels of Bax and caspase‐3 were expressed highly while the mRNA levels of JAM‐2, ERK, BCL‐2, and p38MAPK were lowly expressed in the miR‐374b mimics group. Liao et al () suggested that the dysregulation of miR‐374b expression contributed to angiogenesis in human osteosarcoma cells via ERK and p38 signaling pathways. Qin et al () reported that the activation of ERK and AKT1 pathways may facilitate the CC development.…”

Proangiogenic effects of tumor cells on endothelial progenitor cells vary with tumor type in an in vitro and in vivo rat model

“…Additionally, CINC-2, which is remarkably up-regulated in MCR96 CM, R1H CM, and CC531 CM, has been described to be a dominant factor for hematopoietic progenitor cell mobilization (49). Likewise, MIP-1a, MIP-2, and MIP-3a, all of which belong to the family of chemokines (5,50,51), were significantly up-regulated in MCR86 and R1H CM. These findings are consistent with the observations about the strongest effect on invasion and migration of EPC induced by MCR86 CM in which potent chemotactic factors such as VEGF, MCP-1 (52), MIP-1a, MIP-2, MIP-3a, CINC-2, and MMPs, including MMP-2 and MMP-13 (53), were all significantly up-regulated.…”

A Collagen Based Cryogel Bioscaffold that Generates Oxygen for Islet Transplantation

“…In addition, the EFP from these mice contained a significantly higher amount of insulin compared to mice transplanted with islets only or those seeded into bioscaffolds made from cryogel alone thereby indicating that there was a higher amount of viable and functional β cells within these animals. Furthermore, within the EFP, we also noted an upregulation of MIP‐1α and ‐β,53 IP‐10,54 and IL‐655 (i.e., cytokines which promote angiogenesis) and downregulation of IL‐9,56 LIX,57 and TNF‐α,58 (i.e., cytokines which demonstrate proinflammatory activity) when compared to the control EFP in which islets alone were transplanted. This was further supported by our data which showed decreased inflammation (no TNFα staining) in the histological sections of the EFP containing our cryogel‐0.25 wt%CPO bioscaffolds.…”