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

Ming Yu Lien, An Chen Chang, Hsiao Chi Tsai, Ming Hsui Tsai, Chun Hung Hua, Shih Ping Cheng, Shih Wei Wang, Chih Hsin Tang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

18 Scopus citations

Abstract

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.

Original languageEnglish
Article number592415
JournalFrontiers in Oncology
Volume10
DOIs
StatePublished - 27 11 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© Copyright © 2020 Lien, Chang, Tsai, Tsai, Hua, Cheng, Wang and Tang.

Keywords

  • angiogenesis
  • miR-29c
  • monocyte chemoattractant protein-1
  • oral squamous cell carcinoma
  • vascular endothelial growth factor A

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