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肿瘤驻留周细胞参与口腔鳞状细胞癌。

The participation of tumor residing pericytes in oral squamous cell carcinoma.

机构信息

Department of Oral Surgery, Pathology and Clinical Dentistry, School of Dentistry, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, room 3105, Belo Horizonte, Minas Gerais, CEP: 31.270-901, Brazil.

Biotechnology Post-graduation Program, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.

出版信息

Sci Rep. 2023 Apr 4;13(1):5460. doi: 10.1038/s41598-023-32528-1.

Abstract

Pericytes are perivascular cells related to vessel structure and angiogenesis that can interact with neoplastic cells, interfering with cancer progression and outcomes. This study focused on the characterization of pericytes in oral squamous cell carcinoma (OSCC) using clinical samples and a transgenic mouse model of oral carcinogenesis. Nestin/NG2 (type-1) and nestin/NG2 (type-2) pericytes were analyzed by direct fluorescence after induction of oral carcinogenesis (4-nitroquinoline-1-oxide). Gene expression of neuron glial antigen-2 (NG2), platelet-derived growth factor receptor beta (PDGFR-β), and cluster of differentiation 31 (CD31) was examined in human OSCC tissues. The protein expression of von Willebrand factor and NG2 was assessed in oral leukoplakia (i.e., oral potentially malignant disorders) and OSCC samples. Additionally, clinicopathological aspects and survival data were correlated and validated by bioinformatics using The Cancer Genome Atlas (TCGA). Induction of carcinogenesis in mice produced an increase in both NG2 pericyte subsets. In human OSCC, advanced-stage tumors showed a significant reduction in CD31 mRNA and von Willebrand factor-positive vessels. Low PDGFR-β expression was related to a shorter disease-free survival time, while NG2 mRNA overexpression was associated with a reduction in overall survival, consistent with the TCGA data. Herein, oral carcinogenesis resulted in an increase in NG2 pericytes, which negatively affected survival outcomes.

摘要

周细胞是与血管结构和血管生成有关的血管周围细胞,可与肿瘤细胞相互作用,干扰癌症的进展和结局。本研究使用临床样本和口腔致癌的转基因小鼠模型,重点研究口腔鳞状细胞癌(OSCC)中的周细胞特征。在诱导口腔致癌(4-硝基喹啉-1-氧化物)后,通过直接荧光分析巢蛋白/NG2(1 型)和巢蛋白/NG2(2 型)周细胞。在人 OSCC 组织中检查神经元胶质抗原-2(NG2)、血小板衍生生长因子受体β(PDGFR-β)和分化群 31(CD31)的基因表达。评估口腔白斑(即口腔潜在恶性疾病)和 OSCC 样本中血管性血友病因子和 NG2 的蛋白表达。此外,通过使用癌症基因组图谱(TCGA)进行生物信息学分析,将临床病理方面和生存数据进行相关性和验证。在小鼠中诱导致癌作用会导致两种 NG2 周细胞亚群增加。在人 OSCC 中,晚期肿瘤的 CD31 mRNA 和血管性血友病因子阳性血管明显减少。低 PDGFR-β 表达与无病生存期缩短有关,而 NG2 mRNA 过表达与总生存期缩短有关,与 TCGA 数据一致。在此,口腔致癌作用导致 NG2 周细胞增加,这对生存结局产生负面影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5acb/10073133/a7ec265be6aa/41598_2023_32528_Fig1_HTML.jpg

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