Upregulation of CSF-1 is correlated with elevated TAM infiltration and poor prognosis in oral squamous cell carcinoma

Am J Transl Res. 2020 Oct 15;12(10):6235-6249. eCollection 2020.

Abstract

Mounting lines of evidence indicated that the "colony stimulating factor-1 (CSF-1)/tumor-associated macrophage (TAM)" signature plays an important role in the progression, invasion and metastasis of multiple tumors. However, the potential role of CSF-1/TAM in oral squamous cell carcinoma (OSCC) remains largely unknown. In the present study, the expression of CSF-1 from 99 OSCC specimens and its correlation with clinicopathological features and patient outcomes were investigated. Meanwhile, the correlation between CSF-1 expression and TAM infiltration was also explored. To investigate the potential effect of CSF-1 on tumor growth, nude mice were subcutaneously injected with Cal27 cell line and a small molecule inhibitor of CSF-1 (BZL945). The results showed that the high expression rate of CSF-1 (52%) was found in OSCC, and the upregulation of CSF-1 was closely correlated with lymph node metastasis and clinical stage. Additionally, there was a positive correlation between a high CSF-1 level and elevated TAM infiltration. The xenograft model study showed that CSF-1 signal blockade inhibited tumor growth, with a significant synchronous decrease in CSF-1 expression and TAM infiltration. Overall, our findings indicated that CSF-1 plays a crucial role in TAMs-mediated OSCC tumor progression and invasion. The "CSF-1/TAM" signaling axis may serve as a prospective target for anti-tumor therapy of OSCC.

Keywords: Macrophage colony stimulating factor-1; oral squamous cell carcinoma; tumor microenvironment; tumor-associated macrophages.