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

Cancer Medicine

Manabu Shigeoka³  Naoki Urakawa³  Mari Nishio³  Nobuhisa Takase³  Soken Utsunomiya³  Hiroaki Akiyama³  Yoshihiro Kakeji¹  Takahide Komori²  Yu-ichiro Koma³ 

[1] Division of Gastro-intestinal Surgery, Kobe University Graduate School of Medicine, Kobe, Japan;Division of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan;Division of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan

关键词: CD204;    Cyr61;    esophageal cancer;    macrophage;    tumor microenvironment;   

DOI  :  10.1002/cam4.401

来源: Wiley

【 摘 要 】

Abstract

Tumor-associated macrophages (TAMs) are known to be involved in the progression of various human malignancies. We previously demonstrated that CD204 was a useful marker for TAMs 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 CD204 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 TAMs in ESCC. From the microarray data, we discovered that Cyr61 was induced in CD204-positive-differentiated THP-1 cells (TAM-like THP-1 cells). In the ESCC microenvironment, not only cancer cells but also TAMs expressed Cyr61. Interestingly, the expression levels of Cyr61 showed a significant positive correlation with the number of CD204-positive macrophages in ESCCs by immunohistochemistry. Recombinant human Cyr61 (rhCyr61) promoted cell migration and induced the expression of CD204 along with the activation of the MEK/ERK pathway in MΦ-like THP-1 cells. Pretreatment with a MEK1/2 inhibitor significantly inhibited not only the Cyr61-mediated migration but also the CD204 expression in the MΦ-like THP-1 cells. These results suggest that Cyr61 may contribute to the expression of CD204 and the promotion of cell migration via the MEK/ERK pathway in TAMs in the ESCC microenvironment.

【 授权许可】

CC BY   
© 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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