Monocyte Chemoattractant Protein 1 Promotes VEGF-A Expression in OSCC by Activating ILK and MEK1/2 Signaling and Downregulating miR-29c

• Published in: Frontiers in oncology Vol. 10; p. 592415
• Main Authors: Lien, Ming-Yu, Chang, An-Chen, Tsai, Hsiao-Chi, Tsai, Ming-Hsui, Hua, Chun-Hung, Cheng, Shih-Ping, Wang, Shih-Wei, Tang, Chih-Hsin
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 27.11.2020
• Subjects: angiogenesis; miR-29c; monocyte chemoattractant protein-1; Oncology; oral squamous cell carcinoma; vascular endothelial growth factor A; monocyte chemoattractant protein-1; miR-29c; oral squamous cell carcinoma; vascular endothelial growth factor A; angiogenesis
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2020.592415

Oral squamous cell carcinoma (OSCC) is an aggressive tumor that has a poor prognosis, with high levels of local invasion and lymph node metastasis. Vascular endothelial growth factor A (VEGF-A) plays essential roles in OSCC tumor angiogenesis and metastasis. Monocyte chemoattractant protein-1 (MCP-1, CCL2) is implicated in various inflammatory conditions and pathological processes, including oral cancer. The existing evidence has failed to confirm any correlation between MCP-1 or VEGF-A expression and OSCC angiogenesis. In this study, high expression levels of MCP-1 and VEGF-A were positively correlated with disease stage in patients with OSCC. In oral cancer cells, MCP-1 increased VEGF-A expression and subsequently promoted angiogenesis; miR-29c mimic reversed MCP-1 activity. We also found that MCP-1 modulated VEGF-A expression and angiogenesis through CCR2/ILK/MEK1/2 signaling. Ex vivo results of the chick embryo chorioallantoic membrane (CAM) assay revealed the angiogenic qualities of MCP-1, with increased numbers of visible blood vessel branches. Our data suggest that MCP-1 is a new molecular therapeutic target for the inhibition of angiogenesis and metastasis in OSCC.