抑制原肌球蛋白受体激酶 B 对人雪旺细胞迁移和口腔舌鳞癌细胞体外扩散的影响。
Inhibition of tropomyosine receptor kinase B on the migration of human Schwann cell and dispersion of oral tongue squamous cell carcinoma in vitro.
机构信息
Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida.
Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana.
出版信息
Head Neck. 2019 Dec;41(12):4069-4075. doi: 10.1002/hed.25956. Epub 2019 Sep 9.
BACKGROUND
Schwann cells (SC) may play an important role in perineural invasion (PNI) by promoting cancer cell dispersion. Brain-derived neurotrophic factor (BDNF) may contribute to these cellular events by activating tropomyosine receptor kinase B (TrkB). This study examines the effect of TrkB inhibition on SC migration and oral cancer cell dispersion in vitro.
METHODS
Human tongue squamous cell carcinoma (SCC-9) and human SCs were cocultured in three different conditioned mediums: control, BDNF, and TrkB inhibitor. Cell migration, cancer cell dispersion, and SC dedifferentiation were measured on time-lapse and immunofluorescence images.
RESULTS
Cancer cell migration exceeded SC migration in all conditions. TrkB inhibition promoted SC dedifferentiation and significantly increased SC migration, when compared to BDNF conditions. TrkB inhibition also reduced cancer cell dispersion, when compared to control and BDNF-treated cultures.
CONCLUSION
SCs may have importance in the pathophysiology of PNI. TrkB inhibition may be a potential avenue for therapeutic intervention.
背景
许旺细胞（SC）可能通过促进癌细胞扩散在神经周围浸润（PNI）中发挥重要作用。脑源性神经营养因子（BDNF）可能通过激活原肌球蛋白受体激酶 B（TrkB）促进这些细胞事件。本研究探讨了 TrkB 抑制对体外 SC 迁移和口腔癌细胞扩散的影响。
方法
将人舌鳞癌细胞（SCC-9）与人 SC 共培养在三种不同的条件培养基中：对照、BDNF 和 TrkB 抑制剂。在延时和免疫荧光图像上测量细胞迁移、癌细胞扩散和 SC 去分化。
结果
在所有条件下，癌细胞迁移均超过 SC 迁移。与 BDNF 条件相比，TrkB 抑制促进了 SC 的去分化，并显著增加了 SC 的迁移。与对照和 BDNF 处理的培养物相比，TrkB 抑制也减少了癌细胞的扩散。
结论
SC 可能在 PNI 的病理生理学中具有重要意义。TrkB 抑制可能是一种潜在的治疗干预途径。
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