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Stromal cell-derived factor-1alpha (SDF-1alpha/CXCL12)-enhanced angiogenesis of human basal cell carcinoma cells involves ERK1/2-NF-kappaB/interleukin-6 pathway.
Chu, Chia-Yu; Cha, Shih-Ting; Lin, Wan-Chi; Lu, Po-Hsuan; Tan, Ching-Ting; Chang, Cheng-Chi; Lin, Ben-Ren; Jee, Shiou-Hwa; Kuo, Min-Liang.
Afiliação
  • Chu CY; Department of Dermatology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
Carcinogenesis ; 30(2): 205-13, 2009 Feb.
Article em En | MEDLINE | ID: mdl-18849299
Stromal cell-derived factor 1alpha (SDF-1alpha) (CXCL12) has been observed to enhance tumor angiogenesis. However, the comprehensive role of SDF-1alpha (CXCL12)-CXCR4 interaction, exerted during angiogenesis, has not been well understood. We have previously demonstrated that human basal cell carcinoma (BCC) tissues and a BCC cell line (BCC-1/KMC) had significant expression of CXCR4, whose level was higher in invasive than in the non-invasive BCC types. Here, we observed that human BCC tissues with high expression levels of CXCR4 had higher vascularity. Further, among the 71 BCCs diagnosed between the years 2004-2005, BCCs with high CXCR4 expression had concomitantly higher microvessel density, as compared with those with low CXCR4 expression (P < 0.001). We found that SDF-1alpha induced angiogenic activity in human BCC cells, both in vitro and in vivo. SDF-1alpha significantly upregulated several angiogenesis-associated genes such as interferon-alpha-inducible protein 27, interleukin (IL)-6, bone morphogenetic protein (BMP)-6, SOCS2 and cyclooxygenase 2 (COX)-2 in human BCC cells. Among them, IL-6 was the earliest and highest upregulated gene whose induction was observed within 6 h of the commencement of SDF-1alpha-CXCR4 interaction. The mechanisms behind the SDF-1alpha-induced time and dose-dependent upregulation of messenger RNA expression and protein secretion of IL-6 were investigated. The transcriptional regulation of IL-6 by SDF-1alpha was mediated by phosphorylation of extracellular signal-related kinase 1/2 and activation of the nuclear factor-kappaB complex. The identification of the angiogenic profiles induced through SDF-1alpha-CXCR4 interactions in human BCC cells may contribute further insights into the mechanisms involved in the angiogenic potential of SDF-1alpha (CXCL12).
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / Carcinoma Basocelular / NF-kappa B / Interleucina-6 / Proteína Quinase 1 Ativada por Mitógeno / Proteína Quinase 3 Ativada por Mitógeno / Quimiocina CXCL12 / Neovascularização Patológica Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2009 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / Carcinoma Basocelular / NF-kappa B / Interleucina-6 / Proteína Quinase 1 Ativada por Mitógeno / Proteína Quinase 3 Ativada por Mitógeno / Quimiocina CXCL12 / Neovascularização Patológica Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2009 Tipo de documento: Article