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Relationships of alpha-SMA-positive fibroblasts and SDF-1-positive tumor cells with neoangiogenesis in nasopharyngeal carcinoma.

Wang S, Ma N, Kawanishi S, Hiraku Y, Oikawa S, Xie Y, Zhang Z, Huang G, Murata M - Biomed Res Int (2014)

Bottom Line: The immunoreactive intensities of SDF-1 and CXCR4 were significantly higher in NPC cells.Microvessel density was significantly higher in the stroma of NPC tissues compared to chronic nasopharyngitis tissues.Our data suggest that CAFs and NPC tumor cells may enhance neoangiogenesis in a VEGF- and SDF-1-dependent manner by recruiting EPCs from the bone marrow into tumor stroma.

View Article: PubMed Central - PubMed

Affiliation: Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan ; Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, No. 22 Shuangyong Road, Nanning 530027, China.

ABSTRACT
Nasopharyngeal carcinoma (NPC) is one of the most prevalent malignant tumors with poor prognosis in Southern China and Southeast Asia. Angiogenesis-related molecules can be promising therapeutic targets in NPC. To investigate the relationships of cancer-associated fibroblasts (CAFs) and chemokine-related molecules with neoangiogenesis, we compared immunohistochemical analyses of alpha-smooth-muscle actin (α-SMA), stroma-derived factor-1 (SDF-1), and its receptor CXCR4 in primary NPC specimens and chronic nasopharyngitis tissues. In addition, we examined the expression of vascular endothelial growth factor (VEGF-A), and CD133- and VEGF- receptor-2 (VEGFR-2) double positive cells, as endothelial progenitor cells (EPCs). We also assessed CD34-positive microvessels. Significantly higher expression of α -SMA was observed in fibroblasts in NPC stroma. The immunoreactive intensities of SDF-1 and CXCR4 were significantly higher in NPC cells. CXCR4-positive cells and CD133/VEGFR-2- double positive cells were observed in the stroma surrounding cancer nests, and VEGF was detected in both cancer and stromal cells. Microvessel density was significantly higher in the stroma of NPC tissues compared to chronic nasopharyngitis tissues. Our data suggest that CAFs and NPC tumor cells may enhance neoangiogenesis in a VEGF- and SDF-1-dependent manner by recruiting EPCs from the bone marrow into tumor stroma.

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The expression of SDF-1 and CXCR4 in chronic nasopharyngitis (inflammation) and NPC tissues. (a) The expression of SDF-1 was assessed by immunofluorescence staining (green). Nuclei were counterstained by DAPI (blue). The red dotted line is border between cancer nest and stromal area. HE staining of parallel sections. (b) Immunoperoxidase staining of CXCR4 protein (brown). Original magnification is 200x. Scale bar represents 50 μm. Ca: cancer cells.
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fig2: The expression of SDF-1 and CXCR4 in chronic nasopharyngitis (inflammation) and NPC tissues. (a) The expression of SDF-1 was assessed by immunofluorescence staining (green). Nuclei were counterstained by DAPI (blue). The red dotted line is border between cancer nest and stromal area. HE staining of parallel sections. (b) Immunoperoxidase staining of CXCR4 protein (brown). Original magnification is 200x. Scale bar represents 50 μm. Ca: cancer cells.

Mentions: Figure 2 shows the expression patterns of cancer-specific cytokine SDF-1 and its receptor CXCR4 in primary NPC and chronic nasopharyngitis tissues. In chronic nasopharyngitis tissues (inflammation), epithelial cells showed weak SDF-1 and CXCR4 immunoreactivity (Figures 2(a) and 2(b), left). In primary NPC tissues, SDF-1 was intensively expressed in the cytoplasm and membrane of NPC tumor cells (Figure 2(a), right) and mucosal epithelial cells adjacent to NPC nest (Figure 2(a), middle) but not in the stromal cells (Figure 2(a), right). CXCR4 was strongly expressed in the nucleus, cytoplasm, and cellular membrane of NPC cells and mucosa adjacent to NPC nest (Figure 2(b), middle and right).


Relationships of alpha-SMA-positive fibroblasts and SDF-1-positive tumor cells with neoangiogenesis in nasopharyngeal carcinoma.

Wang S, Ma N, Kawanishi S, Hiraku Y, Oikawa S, Xie Y, Zhang Z, Huang G, Murata M - Biomed Res Int (2014)

The expression of SDF-1 and CXCR4 in chronic nasopharyngitis (inflammation) and NPC tissues. (a) The expression of SDF-1 was assessed by immunofluorescence staining (green). Nuclei were counterstained by DAPI (blue). The red dotted line is border between cancer nest and stromal area. HE staining of parallel sections. (b) Immunoperoxidase staining of CXCR4 protein (brown). Original magnification is 200x. Scale bar represents 50 μm. Ca: cancer cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4020556&req=5

fig2: The expression of SDF-1 and CXCR4 in chronic nasopharyngitis (inflammation) and NPC tissues. (a) The expression of SDF-1 was assessed by immunofluorescence staining (green). Nuclei were counterstained by DAPI (blue). The red dotted line is border between cancer nest and stromal area. HE staining of parallel sections. (b) Immunoperoxidase staining of CXCR4 protein (brown). Original magnification is 200x. Scale bar represents 50 μm. Ca: cancer cells.
Mentions: Figure 2 shows the expression patterns of cancer-specific cytokine SDF-1 and its receptor CXCR4 in primary NPC and chronic nasopharyngitis tissues. In chronic nasopharyngitis tissues (inflammation), epithelial cells showed weak SDF-1 and CXCR4 immunoreactivity (Figures 2(a) and 2(b), left). In primary NPC tissues, SDF-1 was intensively expressed in the cytoplasm and membrane of NPC tumor cells (Figure 2(a), right) and mucosal epithelial cells adjacent to NPC nest (Figure 2(a), middle) but not in the stromal cells (Figure 2(a), right). CXCR4 was strongly expressed in the nucleus, cytoplasm, and cellular membrane of NPC cells and mucosa adjacent to NPC nest (Figure 2(b), middle and right).

Bottom Line: The immunoreactive intensities of SDF-1 and CXCR4 were significantly higher in NPC cells.Microvessel density was significantly higher in the stroma of NPC tissues compared to chronic nasopharyngitis tissues.Our data suggest that CAFs and NPC tumor cells may enhance neoangiogenesis in a VEGF- and SDF-1-dependent manner by recruiting EPCs from the bone marrow into tumor stroma.

View Article: PubMed Central - PubMed

Affiliation: Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan ; Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, No. 22 Shuangyong Road, Nanning 530027, China.

ABSTRACT
Nasopharyngeal carcinoma (NPC) is one of the most prevalent malignant tumors with poor prognosis in Southern China and Southeast Asia. Angiogenesis-related molecules can be promising therapeutic targets in NPC. To investigate the relationships of cancer-associated fibroblasts (CAFs) and chemokine-related molecules with neoangiogenesis, we compared immunohistochemical analyses of alpha-smooth-muscle actin (α-SMA), stroma-derived factor-1 (SDF-1), and its receptor CXCR4 in primary NPC specimens and chronic nasopharyngitis tissues. In addition, we examined the expression of vascular endothelial growth factor (VEGF-A), and CD133- and VEGF- receptor-2 (VEGFR-2) double positive cells, as endothelial progenitor cells (EPCs). We also assessed CD34-positive microvessels. Significantly higher expression of α -SMA was observed in fibroblasts in NPC stroma. The immunoreactive intensities of SDF-1 and CXCR4 were significantly higher in NPC cells. CXCR4-positive cells and CD133/VEGFR-2- double positive cells were observed in the stroma surrounding cancer nests, and VEGF was detected in both cancer and stromal cells. Microvessel density was significantly higher in the stroma of NPC tissues compared to chronic nasopharyngitis tissues. Our data suggest that CAFs and NPC tumor cells may enhance neoangiogenesis in a VEGF- and SDF-1-dependent manner by recruiting EPCs from the bone marrow into tumor stroma.

Show MeSH
Related in: MedlinePlus