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文章:

牙囊细胞与牙周膜细胞对高分化口腔鳞状细胞癌骨侵袭的影响

Impacts of Dental Follicle Cells and Periodontal Ligament Cells on the Bone Invasion of Well-Differentiated Oral Squamous Cell Carcinoma

原文发布日期:3 May 2025

DOI: 10.3390/cancers17091559

类型: Article

开放获取: 是

 

英文摘要:

Background:Oral squamous cell carcinoma (OSCC) frequently invades the jawbone, leading to diagnostic and therapeutic challenges. While tumor–bone interactions have been studied, the specific roles of dental follicle cells (DFCs) and periodontal ligament cells (PDLCs) in OSCC-associated bone resorption remain unclear. This study aimed to compare the effects of DFCs and PDLCs on OSCC-induced bone invasion and elucidate the underlying mechanisms.Methods:Primary human DFCs and PDLCs were isolated from extracted third molars and characterized by Giemsa and immunofluorescence staining. An in vitro co-culture system and an in vivo xenograft mouse model were established using the HSC-2 OSCC cell line. Tumor invasion and osteoclast activation were assessed by hematoxylin and eosin (HE) and tartrate-resistant acid phosphatase (TRAP) staining. Immunohistochemical analysis was performed to evaluate the expression of receptor activator of NF-κB ligand (RANKL) and parathyroid hormone-related peptide (PTHrP).Results:DFCs significantly enhanced OSCC-induced bone resorption by promoting osteoclastogenesis and upregulating RANKL and PTHrP expression. In contrast, PDLCs suppressed RANKL expression and partially modulated PTHrP levels, thereby reducing osteoclast activity.Conclusions:DFCs and PDLCs exert opposite regulatory effects on OSCC-associated bone destruction. These findings underscore the importance of stromal heterogeneity and highlight the therapeutic potential of targeting specific stromal–tumor interactions to mitigate bone-invasive OSCC.

 

摘要翻译: 

背景:口腔鳞状细胞癌(OSCC)常侵犯颌骨,给诊断和治疗带来挑战。尽管肿瘤-骨相互作用已有研究,但牙囊细胞(DFCs)和牙周膜细胞(PDLCs)在OSCC相关骨吸收中的具体作用尚不明确。本研究旨在比较DFCs和PDLCs对OSCC诱导骨侵袭的影响,并阐明其潜在机制。 方法:从拔除的第三磨牙中分离原代人DFCs和PDLCs,通过吉姆萨染色和免疫荧光染色进行鉴定。使用HSC-2 OSCC细胞系建立体外共培养系统和体内异种移植小鼠模型。通过苏木精-伊红(HE)染色和抗酒石酸酸性磷酸酶(TRAP)染色评估肿瘤侵袭和破骨细胞活化情况。采用免疫组织化学分析评估核因子κB受体活化因子配体(RANKL)和甲状旁腺激素相关肽(PTHrP)的表达。 结果:DFCs通过促进破骨细胞生成并上调RANKL和PTHrP表达,显著增强OSCC诱导的骨吸收。相反,PDLCs抑制RANKL表达并部分调节PTHrP水平,从而降低破骨细胞活性。 结论:DFCs和PDLCs对OSCC相关骨破坏具有相反的调节作用。这些发现强调了基质异质性的重要性,并提示靶向特定基质-肿瘤相互作用以减轻骨侵袭性OSCC的治疗潜力。

 

原文链接:

Impacts of Dental Follicle Cells and Periodontal Ligament Cells on the Bone Invasion of Well-Differentiated Oral Squamous Cell Carcinoma

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