RRC ID 66958
著者 Chung MK, Jung YH, Lee JK, Cho SY, Murillo-Sauca O, Uppaluri R, Shin JH, Sunwoo JB.
タイトル CD271 Confers an Invasive and Metastatic Phenotype of Head and Neck Squamous Cell Carcinoma through the Upregulation of Slug.
ジャーナル Clin Cancer Res
Abstract Purpose: Head and neck squamous cell carcinoma (HNSCC) is comprised of heterogeneous populations of cells, and CD271 (NGFR; p75NTR) has been associated with a tumor-initiating cell subpopulation. This study assessed the role of CD271 in modulating metastatic behavior in HNSCC.Experimental Design: CD271 was overexpressed in murine and human oral squamous cell carcinoma cells to assess the impact of CD271 activation on the invasive and metastatic phenotype of these cells, using in vitro and orthotopic in vivo modeling. Treatment with human nerve growth factor (NGF) to activate CD271, as well as shRNA knockdown of the CD271-upregulated Snai2 expression, was used to assess the mechanism of the CD271-induced invasive phenotype. Relevance of CD271 expression in human HNSCC was evaluated in patient-derived xenografts (PDX) and primary human oral cancers, annotated with clinical behavior characteristics and survival data.Results: Forced expression of CD271 resulted in a more invasive and metastatic phenotype. Slug, an epithelial-to-mesenchymal transition (EMT)-related transcription factor, encoded by Snai2, was highly expressed in MOC2-CD271 and HSC3-CD271, compared with respective parental cells. CD271 activation by NGF conferred enhanced invasiveness in CD271-overexpressing cells, which was abrogated by Snai2 knockdown. In PDXs and primary human HNSCC, CD271 expression correlated with higher Snai2 expression, greater nodal metastasis, and shorter disease-free survival.Conclusions: Activation of CD271 results in upregulation of Snai2/Slug, which, in turn, results in a more invasive phenotype and an enhanced capacity for metastasis to regional lymph nodes. These findings point to CD271 as a promising, therapeutic target for oral cancer metastasis. Clin Cancer Res; 24(3); 674-83. ©2017 AACR.
巻・号 24(3)
ページ 674-683
公開日 2018-2-1
DOI 10.1158/1078-0432.CCR-17-0866
PII 1078-0432.CCR-17-0866
PMID 29208672
PMC PMC6713647
MeSH Animals Biomarkers, Tumor Cell Line, Tumor Disease Models, Animal Gene Expression Regulation, Neoplastic* Heterografts Humans Mice Neoplasm Invasiveness Neoplasm Metastasis Neoplasm Staging Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Phenotype Prognosis Receptors, Nerve Growth Factor / genetics Receptors, Nerve Growth Factor / metabolism* Snail Family Transcription Factors / genetics* Snail Family Transcription Factors / metabolism Squamous Cell Carcinoma of Head and Neck / genetics* Squamous Cell Carcinoma of Head and Neck / metabolism* Squamous Cell Carcinoma of Head and Neck / mortality Squamous Cell Carcinoma of Head and Neck / pathology Survival Analysis
IF 10.107
リソース情報
ヒト・動物細胞 HSC-3(RCB1975)