title: Relationships of alpha-SMA-positive fibroblasts and SDF-1-positive tumor cells with neoangiogenesis in nasopharyngeal carcinoma.
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.
authors.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.
authors.forename: Shumin
authors.identifier: 0000-0003-0217-6600
authors.initials: S
authors.lastname: Wang
authors.affiliation: Faculty of Nursing Science, Suzuka University of Medical Science, 3500-3 Minamitamagaki-cho, Suzuka, Mie 513-8670, Japan.
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.affiliation: Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki-cho, Suzuka, Mie 513-8670, Japan.
authors.forename: Shosuke
authors.initials: S
authors.lastname: Kawanishi
authors.affiliation: Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hiraku
authors.affiliation: Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Oikawa
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, No. 22 Shuangyong Road, Nanning 530027, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, No. 22 Shuangyong Road, Nanning 530027, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, No. 22 Shuangyong Road, Nanning 530027, China.
authors.forename: Guangwu
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Mariko
authors.identifier: 0000-0003-3668-7214
authors.initials: M
authors.lastname: Murata
mesh_terms: D000199:Actins / Q000378:metabolism*; D000328:Adult; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002681:China / Q000453:epidemiology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D009363:Neoplasm Proteins