Abstract
Simple SummaryA chondrosarcoma is a common tumor of the bone that has a high propensity to metastasize to distant organs. The effects of NGF in a chondrosarcoma are not confirmed although NGF is capable of promoting the progression and metastasis of several different types of tumors. Here, we found that NGF promotes the chondrosarcoma migration and metastasis in vitro and in vivo. The levels of NGF and MMP-2 in human chondrosarcoma tumor tissues correlated strongly with the tumor stage. We identified that NGF induces the MMP-2 synthesis and chondrosarcoma cell motility by inhibiting miR-423-5p expression through the FAK and c-Src pathways. We suggest that NGF is a worthwhile therapeutic target in the treatment of a metastatic chondrosarcoma.A chondrosarcoma is a common tumor of the soft tissue and bone that has a high propensity to metastasize to distant organs. Nerve growth factor (NGF) is capable of promoting the progression and metastasis of several different types of tumors although the effects of NGF in a chondrosarcoma are not confirmed. Here, we found that the levels of NGF and matrix metalloproteinase-2 (MMP-2) correlated with the tumor stage in patients with a chondrosarcoma. NGF facilitated the MMP-2-dependent cellular migration in human chondrosarcoma JJ012 cells while the overexpression of NGF enhanced the lung metastasis in a mouse model of a chondrosarcoma. NGF promoted the MMP-2 synthesis and cell migration by inhibiting miR-423-5p expression through the FAK and c-Src signaling cascades. NGF appears to be a worthwhile therapeutic target in the treatment of a metastatic chondrosarcoma.
Highlights
A chondrosarcoma is a common tumor of the soft tissue and bone that occurs typically in cartilage-enriched bone [1,2] and has a high propensity to metastasize to distant organs [1]
IHC tissue array results revealed higher levels of Nerve growth factor (NGF) and matrix metalloproteinase-2 (MMP-2) expression in patients with a higher grade chondrosarcoma than in those with a lower grade disease; the levels of NGF and matrix metalloproteinases (MMPs)-2 expression were reflected by the tumor stage (Figure 1A–C)
A positive correlation observed between the MMP-2 and NGF
Summary
A chondrosarcoma is a common tumor of the soft tissue and bone that occurs typically in cartilage-enriched bone (e.g., the femur, tibia or pelvis) [1,2] and has a high propensity to metastasize to distant organs [1]. The metastatic process involves the secretion of proteolytic enzymes such as matrix metalloproteinases (MMPs) and cathepsins, capable of degrading the extracellular matrix (ECM) and basement membrane [5,6]. It is likely that the ECM component alpha-1 type I collagen (col1a1) contributes to the tumor growth as col1a1 is upregulated in various tumors [7] and significantly higher levels of MMP-2 expression have been recorded in human chondrosarcoma specimens than in normal cartilage [8] and increasingly higher levels of MMP-2 expression in human chondrosarcoma cells stimulate their migratory and metastatic potential [7,8]. Chemokine (C-C motif) ligand 3 (CCL3) has been found to increase
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