Cyr61 promotes CD204 expression and the migration of macrophages via MEK/ERK pathway in esophageal squamous cell carcinoma

Abstract Tumor‐associated macrophages ( TAM s) are known to be involved in the progression of various human malignancies. We previously demonstrated that CD 204 was a useful marker for TAM s contributing to the angiogenesis, progression, and prognosis of human esophageal squamous cell carcinoma ( ESCC ). We also showed that conditioned media of ESCC cell lines induced CD 204 expression in THP ‐1 human monocytic leukemia cells. Here, we performed a cDNA microarray analysis between THP ‐1 cells stimulated with TPA (macrophage [MΦ]‐like THP ‐1 cells) treated with and without conditioned medium of ESCC cell line to clarify the molecular characteristics of TAM s in ESCC . From the microarray data, we discovered that Cyr61 was induced in CD 204‐positive‐differentiated THP ‐1 cells ( TAM ‐like THP ‐1 cells). In the ESCC microenvironment, not only cancer cells but also TAM s expressed Cyr61. Interestingly, the expression levels of Cyr61 showed a significant positive correlation with the number of CD 204‐positive macrophages in ESCC s by immunohistochemistry. Recombinant human Cyr61 (rhCyr61) promoted cell migration and induced the expression of CD 204 along with the activation of the MEK / ERK pathway in MΦ‐like THP ‐1 cells. Pretreatment with a MEK 1/2 inhibitor significantly inhibited not only the Cyr61‐mediated migration but also the CD 204 expression in the MΦ‐like THP ‐1 cells. These results suggest that Cyr61 may contribute to the expression of CD 204 and the promotion of cell migration via the MEK / ERK pathway in TAM s in the ESCC microenvironment.