1. Academic Validation
  2. CXCL12/CXCR4 pathway orchestrates CSC-like properties by CAF recruited tumor associated macrophage in OSCC

CXCL12/CXCR4 pathway orchestrates CSC-like properties by CAF recruited tumor associated macrophage in OSCC

  • Exp Cell Res. 2019 May 15;378(2):131-138. doi: 10.1016/j.yexcr.2019.03.013.
Xing Li 1 Wenhuan Bu 2 Lin Meng 2 Xinchen Liu 2 Shuangshuang Wang 1 Liming Jiang 1 Meisi Ren 1 Yu Fan 1 Hongchen Sun 3
Affiliations

Affiliations

  • 1 School and Hospital of Stomatology, China Medical University, Shenyang 110002, PR China.
  • 2 School and Hospital of Stomatology, Jilin University, ChangChun 130021, PR China.
  • 3 School and Hospital of Stomatology, China Medical University, Shenyang 110002, PR China. Electronic address: sunhongchen@cmu.edu.cn.
Abstract

Tumor-associated macrophage (TAM), a crucial component of immune cell infiltrated in tumor microenvironment, is associated with progression of oral squamous cell carcinoma (OSCC). However, it is still unclear how TAM is induced/accumulated and activated around/in OSCC. In the study herein, we tried to understand how TAM accumulates and activates in the OSCC and how TAM promotes OSCC to convert Cancer stem cell (CSC). In this study, first important finding was that the M2 macrophages significantly increased in all twenty human OSCC samples in vivo. Cancer-associated fibroblast (CAF)-derived CXCL12 effectively attracted monocytes, which displayed M2 macrophage phenotype. Blocking CXCL12 receptor (CXCR4) significantly reduced chemotaxis of M2 macrophage. Polarized M2 macrophage promoted CSC-like transition in OSCC cell line, Cal27 cells. These CSC-like cells significantly expressed higher Sox2, Oct4, and Nanog genes, were stronger positive for CD44 and CD105, increased cell proliferation with less Apoptosis, enhanced cell migration, and were resistant to chemotherapy drug, vineristine. These results indicate that CAF effectively attracts monocytes via the CXCL12/CXCR4 pathway and induces their differentiation to M2 macrophages. Interestingly, these polarized M2 macrophages promote formation of CSC-like cells from the OSCC lead to enhance OSCC proliferation with less Apoptosis. Therefore, our findings have potential to lead to novel therapy for the OSCC to target CXCL12-mediated TAM recruitment.

Keywords

CXCL12; Cancer stem cell; Cancer-associated fibroblast; Oral squamous cell carcinoma; Tumor-associated macrophage.

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