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富含细胞贴壁成分的衍生祖细胞对口腔鳞状细胞癌异种移植物生长和新生血管形成的影响。

Influence of buffy coat-derived putative endothelial progenitor cells on tumor growth and neovascularization in oral squamous cell carcinoma xenografts.

机构信息

Interdisciplinary Head & Neck Oncology Laboratory, Department for Oral and Maxillofacial Surgery, University Hospital Giessen and Marburg, Campus Marburg, Baldingerstrasse, D-35033, Marburg, Germany.

Clinic for Oral and Maxillofacial Surgery, University Medical Center Mainz, Mainz, Germany.

出版信息

Clin Oral Investig. 2019 Oct;23(10):3767-3775. doi: 10.1007/s00784-019-02806-2. Epub 2019 Jan 28.

Abstract

OBJECTIVES

The aim of this murine in vivo study was to investigate whether buffy coat-derived putative endothelial progenitor cells (BC) alter tumor growth and neovascularization in oral squamous cell carcinomas (OSCC).

MATERIALS AND METHODS

A murine xenograft model using the PCI-13 oral cancer cell line was deployed of which n = 24 animals received 2 × 10 BC by transfusion whereas the control group (n = 24) received NaCl (0.9%) instead. Tumor size, volume, and capillary density were determined by sonography and measurement with a caliper. Immunohistochemical analysis was carried out with antibodies specific for Cytokeratins, Flt-4, Podoplanin, and Vimentin.

RESULTS

In the experimental group, systemic application of BC significantly increased tumor volume to 362.49% (p = 0.0012) and weight to 352.38% (p = 0.0018) as well as vascular densities to 162.15% (p = 0.0021) compared with control tumors. In addition, BC-treated xenografts exhibited higher Cytokeratin expression levels by a factor of 1.47 (p = 0.0417), Podoplanin by a factor of 3.3 (p = 0.0020) and Vimentin by a factor of 2.5 (p = 0.0001), respectively.

CONCLUSIONS

Immunohistochemical investigations support the notion that BC transfusion influences neovascularization and lymphatic vessel density, thereby possibly promoting tumor progression. Future studies, which will include gene expression analysis, should help to define the possible role of BC during OSCC progression in more detail.

CLINICAL RELEVANCE

Endothelial progenitor cells (EPCs) could serve as a target structure for the treatment of OSCC and possibly other solid tumors.

摘要

目的

本体内研究的目的在于研究富含血液有核细胞的内皮祖细胞(BC)是否能改变口腔鳞状细胞癌(OSCC)中的肿瘤生长和新生血管形成。

材料和方法

采用 PCI-13 口腔癌细胞系建立了小鼠异种移植模型,其中 24 只动物通过输血接受了 2×10 的 BC,而对照组(n=24)接受了生理盐水(0.9%)。通过超声和卡尺测量来确定肿瘤大小、体积和毛细血管密度。采用针对细胞角蛋白、Flt-4、Podoplanin 和波形蛋白的抗体进行免疫组织化学分析。

结果

在实验组中,BC 的全身应用使肿瘤体积增加到 362.49%(p=0.0012),重量增加到 352.38%(p=0.0018),血管密度增加到 162.15%(p=0.0021),与对照组相比。此外,BC 处理的异种移植物的细胞角蛋白表达水平增加了 1.47 倍(p=0.0417),Podoplanin 增加了 3.3 倍(p=0.0020),波形蛋白增加了 2.5 倍(p=0.0001)。

结论

免疫组织化学研究支持这样的观点,即 BC 输注会影响新生血管形成和淋巴管密度,从而可能促进肿瘤的进展。未来的研究,包括基因表达分析,将有助于更详细地定义 BC 在 OSCC 进展过程中的可能作用。

临床相关性

内皮祖细胞(EPCs)可作为治疗 OSCC 及其他实体瘤的靶结构。

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