title: Cyr61 promotes CD204 expression and the migration of macrophages via MEK/ERK pathway in esophageal squamous cell carcinoma.
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.
authors.affiliation: Division of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan; Division of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Shigeoka
authors.forename: Naoki
authors.initials: N
authors.lastname: Urakawa
authors.forename: Mari
authors.initials: M
authors.lastname: Nishio
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Takase
authors.forename: Soken
authors.initials: S
authors.lastname: Utsunomiya
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Akiyama
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kakeji
authors.forename: Takahide
authors.initials: T
authors.lastname: Komori
authors.forename: Yu-ichiro
authors.initials: Y
authors.lastname: Koma
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yokozaki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D055515:Cysteine-Rich Protein 61 / Q000235:genetics / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism*
chemical_list: C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; C495139:MSR1 protein, human; D051117:Scavenger Receptors, Class A
keywords: CD204; Cyr61; esophageal cancer; macrophage; tumor microenvironment