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Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
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Targeting CCL2-CCR4 axis suppress cell migration of head and neck squamous cell carcinoma

Zihang Ling1,2, Wei Li1,2, Jiaqi Hu1,2

  • 1Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510055, P. R. China.

Cell Death & Disease
|February 18, 2022
PubMed

Insights

Targeting C-C motif chemokine ligand 2 (CCL2) and C-C motif chemokine receptor 4 (CCR4) signaling inhibits head and neck squamous cell carcinoma (HNSCC) metastasis. This pathway, involving Vav2-Rac1-p-MLC, offers a potential therapeutic target for HNSCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Head and neck squamous cell carcinoma (HNSCC) mortality is primarily driven by local invasion and distant metastasis.
  • Chemokines and their receptors are critical regulators of cancer cell migration and metastasis, making them attractive therapeutic targets.

Purpose of the Study:

  • To investigate the role of C-C motif chemokine ligand 2 (CCL2) signaling pathways in HNSCC invasion and metastasis.
  • To identify potential molecular targets for interrupting HNSCC metastasis.

Main Methods:

  • Analysis of the CCL2-C-C motif chemokine receptor 4 (CCR4) and CCL2-C-C motif chemokine receptor 2 (CCR2) signaling axes.
  • Investigation of the formation of the vav guanine nucleotide exchange factor 2 (Vav2)-Rac family small GTPase 1 (Rac1) complex.
  • Assessment of myosin light chain (MLC) phosphorylation as a downstream effect.

Main Results:

  • The CCL2-CCR4 axis, not CCL2-CCR2, induced Vav2-Rac1 complex formation and subsequent MLC phosphorylation.
  • Targeting CCR4 effectively inhibited CCL2-induced HNSCC invasion and metastasis.
  • No cancer relapse was observed after CCR4 inhibition withdrawal.

Conclusions:

  • The CCL2-CCR4-Vav2-Rac1-p-MLC signaling pathway is crucial for HNSCC cell migration and metastasis.
  • CCR4 represents a promising molecular target for HNSCC therapy, potentially offering a durable therapeutic effect without promoting relapse.

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