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

Shigeoka M, Urakawa N, Nishio M, Takase N, Utsunomiya S, Akiyama H, Kakeji Y, Komori T, Koma Y, Yokozaki H - Cancer Med (2015)

Bottom Line: Tumor-associated macrophages (TAMs) are known to be involved in the progression of various human malignancies.Interestingly, the expression levels of Cyr61 showed a significant positive correlation with the number of CD204-positive macrophages in ESCCs by immunohistochemistry.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.

View Article: PubMed Central - PubMed

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.

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Expression of Cyr61 in the ESCC microenvironment. (A) Immunofluorescence of Cyr61 and CD204 in ESCC tissues. Cyr61 (green) was expressed in cancer nests and stroma. CD204 (red)-positive MΦ with Cyr61 expression was observed in cancer nests and stroma. Scale bar, 50 μm. (B and C) Expression of Cyr61 in ESCC cell lines. Five ESCC cell lines (TE-8, TE-9, TE-10, TE-11, and TE-15) demonstrated Cyr61 mRNA expression (B, RT-PCR) and protein secretion (C, ELISA). Error bars indicate SEM. (D) Representative immunoreaction of high- and low-Cyr61 expression in the nests of ESCCs. In the high-Cyr61 group, the immunoreaction of Cyr61 was stronger than that in the corresponding nonneoplastic esophageal epithelium (i). In the low-Cyr61 group, the expression level of Cyr61 in the cancer nests was equal to that of the corresponding nonneoplastic esophageal epithelium (ii). Scale bar, 100 μm. ELISA, enzyme-linked immunosorbent assay.
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fig02: Expression of Cyr61 in the ESCC microenvironment. (A) Immunofluorescence of Cyr61 and CD204 in ESCC tissues. Cyr61 (green) was expressed in cancer nests and stroma. CD204 (red)-positive MΦ with Cyr61 expression was observed in cancer nests and stroma. Scale bar, 50 μm. (B and C) Expression of Cyr61 in ESCC cell lines. Five ESCC cell lines (TE-8, TE-9, TE-10, TE-11, and TE-15) demonstrated Cyr61 mRNA expression (B, RT-PCR) and protein secretion (C, ELISA). Error bars indicate SEM. (D) Representative immunoreaction of high- and low-Cyr61 expression in the nests of ESCCs. In the high-Cyr61 group, the immunoreaction of Cyr61 was stronger than that in the corresponding nonneoplastic esophageal epithelium (i). In the low-Cyr61 group, the expression level of Cyr61 in the cancer nests was equal to that of the corresponding nonneoplastic esophageal epithelium (ii). Scale bar, 100 μm. ELISA, enzyme-linked immunosorbent assay.

Mentions: Cyr61 has been reported to be expressed in normal squamous epithelia and upregulated in tumor cells of squamous cell carcinoma,23,24 but its expression in stromal cells including macrophages has not been well established. We thus investigated the expression of Cyr61 in ESCC tissues by immunofluorescence (Fig.2A). The expression of Cyr61 was detected not only in cancer nests but also in stromal cells with macrophage-like morphology. Interestingly, a part of the Cyr61+ stromal cells also demonstrated CD204 immunoreactivity. Moreover, CD204+ macrophages with Cyr61 expression were evidently present within the cancer nests (Fig.2A, arrows). We also confirmed the expression of Cyr61 at the mRNA and secreted protein levels in all five ESCC cell lines (Figs.2B and C).


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

Shigeoka M, Urakawa N, Nishio M, Takase N, Utsunomiya S, Akiyama H, Kakeji Y, Komori T, Koma Y, Yokozaki H - Cancer Med (2015)

Expression of Cyr61 in the ESCC microenvironment. (A) Immunofluorescence of Cyr61 and CD204 in ESCC tissues. Cyr61 (green) was expressed in cancer nests and stroma. CD204 (red)-positive MΦ with Cyr61 expression was observed in cancer nests and stroma. Scale bar, 50 μm. (B and C) Expression of Cyr61 in ESCC cell lines. Five ESCC cell lines (TE-8, TE-9, TE-10, TE-11, and TE-15) demonstrated Cyr61 mRNA expression (B, RT-PCR) and protein secretion (C, ELISA). Error bars indicate SEM. (D) Representative immunoreaction of high- and low-Cyr61 expression in the nests of ESCCs. In the high-Cyr61 group, the immunoreaction of Cyr61 was stronger than that in the corresponding nonneoplastic esophageal epithelium (i). In the low-Cyr61 group, the expression level of Cyr61 in the cancer nests was equal to that of the corresponding nonneoplastic esophageal epithelium (ii). Scale bar, 100 μm. ELISA, enzyme-linked immunosorbent assay.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig02: Expression of Cyr61 in the ESCC microenvironment. (A) Immunofluorescence of Cyr61 and CD204 in ESCC tissues. Cyr61 (green) was expressed in cancer nests and stroma. CD204 (red)-positive MΦ with Cyr61 expression was observed in cancer nests and stroma. Scale bar, 50 μm. (B and C) Expression of Cyr61 in ESCC cell lines. Five ESCC cell lines (TE-8, TE-9, TE-10, TE-11, and TE-15) demonstrated Cyr61 mRNA expression (B, RT-PCR) and protein secretion (C, ELISA). Error bars indicate SEM. (D) Representative immunoreaction of high- and low-Cyr61 expression in the nests of ESCCs. In the high-Cyr61 group, the immunoreaction of Cyr61 was stronger than that in the corresponding nonneoplastic esophageal epithelium (i). In the low-Cyr61 group, the expression level of Cyr61 in the cancer nests was equal to that of the corresponding nonneoplastic esophageal epithelium (ii). Scale bar, 100 μm. ELISA, enzyme-linked immunosorbent assay.
Mentions: Cyr61 has been reported to be expressed in normal squamous epithelia and upregulated in tumor cells of squamous cell carcinoma,23,24 but its expression in stromal cells including macrophages has not been well established. We thus investigated the expression of Cyr61 in ESCC tissues by immunofluorescence (Fig.2A). The expression of Cyr61 was detected not only in cancer nests but also in stromal cells with macrophage-like morphology. Interestingly, a part of the Cyr61+ stromal cells also demonstrated CD204 immunoreactivity. Moreover, CD204+ macrophages with Cyr61 expression were evidently present within the cancer nests (Fig.2A, arrows). We also confirmed the expression of Cyr61 at the mRNA and secreted protein levels in all five ESCC cell lines (Figs.2B and C).

Bottom Line: Tumor-associated macrophages (TAMs) are known to be involved in the progression of various human malignancies.Interestingly, the expression levels of Cyr61 showed a significant positive correlation with the number of CD204-positive macrophages in ESCCs by immunohistochemistry.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.

View Article: PubMed Central - PubMed

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.

Show MeSH
Related in: MedlinePlus