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评估人牙髓间充质干细胞分泌组对人口腔癌细胞系、乳腺癌细胞系和黑色素瘤细胞系的影响。

Assessing the effect of human dental pulp mesenchymal stem cell secretome on human oral, breast, and melanoma cancer cell lines.

作者信息

Raj A Thirumal, Kheur Supriya, Bhonde Ramesh, Mani Vishnu R, Baeshen Hosam Ali, Patil Shankargouda

机构信息

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

Dr.D.Y.Patil Vidyapeeth, Pune, India.

出版信息

Saudi J Biol Sci. 2021 Nov;28(11):6556-6567. doi: 10.1016/j.sjbs.2021.07.029. Epub 2021 Jul 14.

Abstract

BACKGROUND

The secretome of the dental pulp mesenchymal stem cells (DPMSCS-S) have an array of regenerative potential and could aid in the rehabilitation of cancer patients post-therapeutic interventions, although caution is required as DPMSC-S have shown to augment prostate cancer cells. Thus, it is vital to assess if these pro-carcinogenic effects extend to other cancer types.

OBJECTIVE

To assess if DPMSC-S has any pro-carcinogenic effect on oral cancer, breast cancer, and melanoma cell lines.

MATERIALS AND METHODS

Conditioned media obtained from the isolated and characterized DPMSC (DPMSC-CM) were profiled using bead-based multiplex assay. AW13515 (oral cancer), MDA-MB-231 (breast cancer), and A-375 (melanoma) cell lines were exposed to 20%, 50%, and 100% DPMSC-CM for 24, 48, and 72 h. DPMSC-CM effect on the cancer cell properties and secretome were assessed.

RESULTS

DPMSC-CM augmented invasion, adhesion, multi-drug resistance, DNA repair, and mitochondrial repair in AW13516 through upregulation of growth factors Ang-2, EGF, M-CSF, PDGF-AA, PDGF-BB, pro-inflammatory cytokines TNF-α, IL-2, downregulation of anti-inflammatory cytokine TGF-β1, and pro-inflammatory cytokine IL-4. In MDA-MB-231, invasion, and multi-drug resistance were augmented through upregulation of growth factors EGF, EPO, G-CSF, HGF, M-CSF, PDGF-AA, and pro-inflammatory cytokine TNF-α, CXCL10, IL-12p70. EMT, invasion, migration, and adhesion were augmented in A-375 through upregulation of growth factors Ang-2, EGF, PDGF-BB, TGF-α, pro-inflammatory cytokines TNF-α, and IL-17A.

CONCLUSION

DPMSC-CM can augment the carcinogenic properties of oral cancer, breast cancer, and melanoma cells, further animal model studies are required to validate our in-vitro findings.

摘要

背景

牙髓间充质干细胞的分泌组(DPMSCS-S)具有一系列再生潜力,有助于癌症患者在治疗干预后的康复,不过由于已证明DPMSC-S会促进前列腺癌细胞生长,所以需要谨慎对待。因此,评估这些促癌作用是否会扩展到其他癌症类型至关重要。

目的

评估DPMSC-S对口腔癌、乳腺癌和黑色素瘤细胞系是否有促癌作用。

材料和方法

使用基于磁珠的多重分析方法对从分离并鉴定的DPMSC获得的条件培养基(DPMSC-CM)进行分析。将AW13515(口腔癌)、MDA-MB-231(乳腺癌)和A-375(黑色素瘤)细胞系分别暴露于20%、50%和100%的DPMSC-CM中24、48和72小时。评估DPMSC-CM对癌细胞特性和分泌组的影响。

结果

DPMSC-CM通过上调生长因子Ang-2、EGF、M-CSF、PDGF-AA、PDGF-BB、促炎细胞因子TNF-α、IL-2,下调抗炎细胞因子TGF-β1和促炎细胞因子IL-4,增强了AW13516中的侵袭、黏附、多药耐药、DNA修复和线粒体修复。在MDA-MB-231中,通过上调生长因子EGF、EPO、G-CSF、HGF、M-CSF、PDGF-AA和促炎细胞因子TNF-α、CXCL10、IL-12p70,增强了侵袭和多药耐药。在A-375中,通过上调生长因子Ang-2、EGF、PDGF-BB、TGF-α、促炎细胞因子TNF-α和IL-17A,增强了EMT、侵袭、迁移和黏附。

结论

DPMSC-CM可增强口腔癌、乳腺癌和黑色素瘤细胞的致癌特性,需要进一步的动物模型研究来验证我们的体外研究结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7b/8568833/e539ea95dd80/gr1.jpg

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