Abstract
Tumor-associated macrophages (TAMs) promote cancer cell proliferation and metastasis, as well as anti-tumor immune suppression. Recent studies have shown that tumors enhance the recruitment and differentiation of TAMs, but the detailed mechanisms have not been clarified. We thus examined the influence of cancer cells on the differentiation of monocytes to TAM subsets, including CD163+, CD204+, and CD206+ cells, in oral squamous cell carcinoma (OSCC) using immunohistochemistry, flow cytometry, and a cytokine array. Furthermore, we investigated the effect of OSCC cells (HSC-2, SQUU-A, and SQUU-B cells) on the differentiation of purified CD14+ cells to TAM subsets. The localization patterns of CD163+, CD204+, and CD206+ in OSCC sections were quite different. The expression of CD206 on CD14+ cells was significantly increased after the co-culture with OSCC cell lines, while the expressions of CD163 and CD204 on CD14+ cells showed no change. High concentrations of plasminogen activator inhibitor-1 (PAI-1) and interleukin-8 (IL-8) were detected in the conditioned medium of OSCC cell lines. PAI-1 and IL-8 stimulated CD14+ cells to express CD206. Moreover, there were positive correlations among the numbers of CD206+, PAI-1+, and IL-8+ cells in OSCC sections. These results suggest that PAI-1 and IL-8 produced by OSCC contribute to the differentiation of monocytes to CD206+ TAMs.
Highlights
Oral squamous cell carcinoma (OSCC) represents approximately 90% of all malignant neoplasms of the head and neck and is associated with a high mortality rate
We further performed triple immunofluorescence staining to confirm the distribution of these Tumor-associated macrophages (TAMs) markers in OSCC tissues, and it was different from its distribution (Figure 1B)
We examined the localizations of plasminogen activator inhibitor-1 (PAI-1) and IL-8 in the OSCC section
Summary
Oral squamous cell carcinoma (OSCC) represents approximately 90% of all malignant neoplasms of the head and neck and is associated with a high mortality rate. More than 400,000 people are affected by OSCC per year worldwide, and the five-year survival rate of advanced-stage OSCC has remained low for decades because of its rapid progression and high metastasis and recurrence capability [1,2,3,4,5]. A better understanding of the mechanisms underlying the initiation, progression, and metastasis of OSCC is required to identify potential treatments to improve the poor outcome of this disease. TAMs are considered the most potent factor that contribute toward tumor cell proliferation, metastasis, and angiogenesis [10]. Tumors secrete exogenous factors that enhance the chemotaxis/migration of monocytes and the differentiation of monocytes to TAMs in the TME [11]. We investigated the effect of OSCC tumor cell-soluble factors on the differentiation of monocytes to TAMs in vitro and identified the distinct soluble factors that influence monocyte differentiation
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