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原肌球蛋白相关激酶B(TrkB)在头颈癌中的意义。

Implications of tropomyosin-related kinase B (TrkB) in head and neck cancer.

作者信息

Zhu Li, Werner Jochen A, Mandic Robert

机构信息

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Giessen and Marburg, Campus Marburg, Marburg, Germany.

出版信息

Anticancer Res. 2007 Sep-Oct;27(5A):3121-6.

Abstract

BACKGROUND

Head and neck squamous cell carcinomas (HNSCC) represent the most common malignancies of the upper aerodigestive tract. Expression of tropomyosin-related kinase B (TrkB) was found to be essential to prevent anoikis in rat intestinal epithelial cells allowing for survival of cells outside the epithelial cell layer and subsequent metastatic spread. The aim of the present study was to examine the potential role of TrkB in HNSCC disease.

MATERIALS AND METHODS

SDS-PAGE and Western blot analysis of TrkB expression were performed under standard conditions. Immunohistochemistry was performed with the Avidin Biotin Complex method, whereas immunocytochemistry was performed by fluorescence staining. Tumor cell invasiveness was measured by an in vitro invasion assay.

RESULTS

A variable but consistent expression of TrkB could be observed in HNSCC tissues and cell lines, whereas no significant expression was seen in the healthy control tissue (soft palate). Immunohisto- and cytochemical staining further demonstrated pronounced TrkB expression in HNSCC tumor cells. However, the invasive properties of TrkB-expressing HNSCC cells were not significantly altered after treatment with 10 or 100 ng/ml brain-derived neurotrophic factor, the natural ligand of TrkB.

CONCLUSION

The presented data implicates to a great extent that TrkB plays a significant role in HNSCC disease since it was consistently found to be overexpressed in cells of this tumor entity. We conclude that the role of this receptor tyrosine kinase is rather the prevention of anoikis, as demonstrated earlier, and less the modulation of HNSCC invasiveness, since invasion was not affected after receptor stimulation. Further studies should investigate possible inhibitors of TrkB and their suitability for the treatment of head and neck cancer.

摘要

背景

头颈部鳞状细胞癌(HNSCC)是上呼吸消化道最常见的恶性肿瘤。已发现原肌球蛋白相关激酶B(TrkB)的表达对于防止大鼠肠道上皮细胞发生失巢凋亡至关重要,这使得上皮细胞层外的细胞得以存活并随后发生转移扩散。本研究的目的是探讨TrkB在HNSCC疾病中的潜在作用。

材料与方法

在标准条件下进行TrkB表达的SDS-PAGE和蛋白质印迹分析。采用抗生物素蛋白-生物素复合物法进行免疫组织化学检测,而免疫细胞化学检测则通过荧光染色进行。通过体外侵袭试验测量肿瘤细胞的侵袭性。

结果

在HNSCC组织和细胞系中可观察到TrkB表达存在差异但较为一致,而在健康对照组织(软腭)中未见明显表达。免疫组织化学和细胞化学染色进一步证明HNSCC肿瘤细胞中TrkB表达明显。然而,用TrkB的天然配体10或100 ng/ml脑源性神经营养因子处理后,表达TrkB的HNSCC细胞的侵袭特性未发生明显改变。

结论

所呈现的数据在很大程度上表明TrkB在HNSCC疾病中起重要作用,因为在该肿瘤实体的细胞中一直发现其过度表达。我们得出结论,这种受体酪氨酸激酶的作用更多的是如先前所示防止失巢凋亡,而较少调节HNSCC的侵袭性,因为受体刺激后侵袭未受影响。进一步的研究应探究TrkB的可能抑制剂及其对头颈部癌治疗的适用性。

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