Squamous cell carcinoma induce phenotypic and genomic changes in macrophages

Background and objectives: Tumour associated inflammation is a major driving force in the progression of squamous cell carcinoma (SCC), the most common caner in head and neck. The aim of the present study is to investigate that whether SCC cells could affected the inflammatory environment by interaction with monocytes.

Methods: Monocytes (THP-1) stained with PKH26 were exposed to SCC cells (CAL-27) and adenoid cystic carcinoma (ACC) cells (SACC-83), followed by FACS analyses and detection of monocyte-to-marcophage differentiation, polarization, attachment and gene expression by real time PCR. Changes induced by co-culture were compared with that observed under classical differentiation and polarization conditions. Immunohistochemical staining was performed to evaluate the expression level of CD68 in SCC and ACC tissues (as a control for non-inflammatory tumour).

Results: In vitro studies revealed that THP-1 cells co-cultured with CAL-27 had more significantly altered gene expression with up-regulation of both M1 and M2 macrophage markers (IL-1alpha, IL-6, TNF-alpha, and MMP-9), than that co-cultured with SACC-83. Compared to SACC-83, CAL-27 induced more THP-1 cells to attach and differentiate into macrophages. THP-1 that co-cultured with CAL-27 expressed higher levels of CXCR4 than with SACC-83. Moreover, more extensive chemokine SDF-1alpha was detected in the co-cultured CAL-27 rather than SACC-83 cells. The co-culture system containing AMD3100 significantly suppressed THP-1 cells attachment and differentiation. The immunohistochemical results revealed that much more expression of CD68+ macrophages in SCC tissues than that in ACC.

Conclusions: Compared to non-inflammatory cancer, SCC, as an inflammatory tumour, showed enhanced abilities in recruiting and inducing differentiation of monocytes, which indicated that inflammation in such tumours may be the nature of itself rather than induced by external factors.

Key words: inflammation; cancer; macrophages; co-culture; SDF-1alpha

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Jan 21, 2018 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Squamous cell carcinoma induce phenotypic and genomic changes in macrophages
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