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牙髓间充质干细胞分泌组中的生长因子和细胞因子可能有助于口腔癌的增殖。

The Growth Factors and Cytokines of Dental Pulp Mesenchymal Stem Cell Secretome May Potentially Aid in Oral Cancer Proliferation.

机构信息

Department of Oral Pathology and Microbiology, Dr. D.Y. Patil Dental College and Hospital, Dr. D.Y. Patil Vidyapeeth, Pune 411018, India.

Department of Prosthodontics and Dental Implantology, College of Dentistry, King Faisal University, Al-Ahsa 31982, Saudi Arabia.

出版信息

Molecules. 2021 Sep 19;26(18):5683. doi: 10.3390/molecules26185683.

Abstract

BACKGROUND

Growth factors and cytokines responsible for the regenerative potential of the dental pulp mesenchymal stem cell secretome (DPMSC-S) are implicated in oral carcinogenesis. The impact and effects of these secretory factors on cancer cells must be understood in order to ensure their safe application in cancer patients.

OBJECTIVE

We aimed to quantify the growth factors and cytokines in DPMSC-S and assess their effect on oral cancer cell proliferation.

MATERIALS AND METHODS

DPMSCs were isolated from patients with healthy teeth ( = 5) that were indicated for extraction for orthodontic reasons. The cells were characterized using flow cytometry and conditioned medium (DPMSC-CM) was prepared. DPMSC-CM was subjected to a bead-based array to quantify the growth factors and cytokines that may affect oral carcinogenesis. The effect of DPMSC-CM (20%, 50%, 100%) on the proliferation of oral cancer cells (AW123516) was evaluated using a Ki-67-based assay at 48 h. AW13516 cultured in the standard growth medium acted as the control.

RESULTS

VEGF, HCF, Ang-2, TGF-α, EPO, SCF, FGF, and PDGF-BB were the growth factors with the highest levels in the DPMSC-CM. The highest measured pro-inflammatory cytokine was TNF-α, followed by CXCL8. The most prevalent anti-inflammatory cytokine in the DPMSC-CM was IL-10, followed by TGF-β1 and IL-4. Concentrations of 50% and 100% DPMSC-CM inhibited Ki-67 expression in AW13516, although the effect was non-significant. Moreover, 20% DPMSC-CM significantly increased Ki-67 expression compared to the control.

CONCLUSIONS

The increased Ki-67 expression of oral cancer cells in response to 20% DPMSC-CM indicates the potential for cancer progression. Further research is needed to identify their effects on other carcinogenic properties, including apoptosis, stemness, migration, invasion, adhesion, and therapeutic resistance.

摘要

背景

负责牙髓间充质干细胞 secretome(DPMSC-S)再生潜力的生长因子和细胞因子与口腔癌发生有关。为了确保这些分泌因子在癌症患者中的安全应用,必须了解这些分泌因子对癌细胞的影响和作用。

目的

我们旨在定量 DPMSC-S 中的生长因子和细胞因子,并评估它们对口腔癌细胞增殖的影响。

材料和方法

从因正畸原因需要拔牙的健康牙齿患者中分离 DPMSCs(n=5)。使用流式细胞术对细胞进行特征分析,并制备条件培养基(DPMSC-CM)。DPMSC-CM 进行珠基阵列以定量可能影响口腔癌变的生长因子和细胞因子。使用基于 Ki-67 的测定法在 48 h 评估 DPMSC-CM(20%、50%、100%)对口腔癌细胞(AW123516)增殖的影响。AW13516 在标准生长培养基中培养作为对照。

结果

DPMSC-CM 中含量最高的生长因子为 VEGF、HCF、Ang-2、TGF-α、EPO、SCF、FGF 和 PDGF-BB。测量到的最高促炎细胞因子是 TNF-α,其次是 CXCL8。DPMSC-CM 中最常见的抗炎细胞因子是 IL-10,其次是 TGF-β1 和 IL-4。50%和 100% DPMSC-CM 浓度抑制了 AW13516 中的 Ki-67 表达,但无统计学意义。此外,与对照组相比,20% DPMSC-CM 显著增加了 Ki-67 表达。

结论

口腔癌细胞对 20% DPMSC-CM 的 Ki-67 表达增加表明癌症进展的潜力。需要进一步研究以确定它们对其他致癌特性的影响,包括细胞凋亡、干细胞特性、迁移、侵袭、黏附和治疗抵抗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5da/8466568/9d1ee9c33657/molecules-26-05683-g001.jpg

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