Antitumor effects of conditioned media of human fetal dermal mesenchymal stem cells on melanoma cells
Antitumor effects of conditioned media of human fetal dermal mesenchymal stem cells on melanoma cells
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人胎真皮间充质干细胞条件培养基对黑色素瘤细胞的抗肿瘤作用
DOI：
10.2147/ott.s203910
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发表时间：
2019-05
影响因子：
4
通讯作者：
Duyin Jiang
中科院分区：
文献类型：
--
作者：
Bencheng Sun;Xiao Wang;Yi Pan;Ya Jiao;Yongjun Qi;Hongmin Gong;Duyin Jiang
背景：恶性黑色素瘤是最致命的皮肤肿瘤，具有高转移率和运动能力。由于预后差，寻求有效的治疗方案是当务之急。人类间充质干细胞（MSC）可以归巢肿瘤细胞，并已被证明在促进和抑制肿瘤发展方面发挥重要作用。胎儿真皮间充质干细胞（FDMSCs）来源于胎儿皮肤，是一种新型的间充质干细胞来源。然而，FDMSCs对恶性黑色素瘤的抗肿瘤能力尚不清楚。材料与方法：从胎儿背部皮肤组织中分离FDMSCs。A375黑素瘤细胞系获自美国典型培养物保藏中心。在体内使用肿瘤形成测定和体外使用细胞活力、5-乙炔基-2-脱氧尿苷掺入、流式细胞术、TdT介导的dUTP缺口末端标记（TUNEL）、伤口愈合、transwell侵袭和Western印迹测试来自FDMSC的条件培养基（CM-FDMSC）对A375黑素瘤细胞的作用。结果：CM-FDMSC在体内抑制A375肿瘤形成。在体外，CM-FDMSC抑制A375黑色素瘤细胞的肿瘤相关活性，如证明活力、迁移和侵袭的降低。CM-FDMSC处理的A375细胞表现出磷脂酰肌醇3-激酶（PI 3 K）、蛋白激酶B（AKT）和细胞外信号调节激酶（ERK）磷酸化的降低，以及Bcl-2相关X（BAX）的上调和B细胞淋巴瘤-2（BCL-2）表达的下调。结论：CM-FDMSC可抑制A375黑色素瘤细胞的成瘤行为，并抑制PI 3 K/AKT和丝裂原活化蛋白激酶信号传导，使其BCL-2/BAX比率向促凋亡状态转变。鉴定CM-FDMSC中的生物活性成分对于将这些发现转化为恶性黑色素瘤的新疗法将是重要的。
Background: Malignant melanoma is the most lethal form of cutaneous tumor and has a high metastatic rate and motility capacity. Owing to the poor prognosis, it is urgent to seek an effective therapeutic regimen. Human mesenchymal stem cells (MSCs) can home to tumor cells and have been shown to play important roles in both promoting and inhibiting tumor development. Fetal dermal MSCs (FDMSCs), derived from fetal skin are a novel source of MSCs. Nevertheless, the antitumor capacity of FDMSCs on malignant melanoma is not clearly understood. Materials and methods: FDMSCs were extracted from the dorsal skin of fetal tissues. A375 melanoma cells lines were obtained from American Type Culture Collection. The effects of conditioned media from FDMSCs (CM-FDMSC) on A375 melanoma cells were tested in vivo using tumor formation assay and in vitro using cell viability, 5-ethynyl-2ʹ-deoxyuridine incorporation, flow cytometry, TdT-mediated dUTP Nick-End Labeling (TUNEL), wound healing, transwell invasion, and Western blotting. Results: CM-FDMSC inhibited A375 tumor formation in vivo. In vitro, CM-FDMSC inhibited the tumor-related activities of A375 melanoma cells, as evidenced reductions in viability, migration, and invasion. CM-FDMSC-treated A375 cells showed decreased phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and extracellular signal-regulated kinase (ERK) phosphorylation, and up-regulation of Bcl-2-Associated X (BAX) and down-regulation of B-cell lymphoma-2 (BCL-2) expression. Conclusion: CM-FDMSC can inhibit the tumor-forming behaviors of A375 melanoma cells and inhibit PI3K/AKT and mitogen-activated protein kinase signaling to shift their BCL-2/BAX ratio toward a proapoptotic state. Identification of the bioactive components in CM-FDMSC will be important for translating these findings into novel therapies for malignant melanoma.
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DOI：
10.1016/b978-1-4160-3251-9.50008-x
发表时间：
2019-10
期刊：
The Lancet
影响因子：
--
作者：
E. Dekker;P. Tanis;J. Vleugels;P. Kasi;M. Wallace
通讯作者：
E. Dekker;P. Tanis;J. Vleugels;P. Kasi;M. Wallace
无疤痕胎儿伤口愈合：基础科学评论。
影响因子：
3.6
作者：
Larson BJ;Longaker MT;Lorenz HP
通讯作者：
Lorenz HP
影响因子：
5.7
作者：
Liu C;Feng X;Wang B;Wang X;Wang C;Yu M;Cao G;Wang H
通讯作者：
Wang H
影响因子：
11.2
作者：
Brighton HE;Angus SP;Bo T;Roques J;Tagliatela AC;Darr DB;Karagoz K;Sciaky N;Gatza ML;Sharpless NE;Johnson GL;Bear JE
通讯作者：
Bear JE
影响因子：
7.5
作者：
Han I;Yun M;Kim EO;Kim B;Jung MH;Kim SH
通讯作者：
Kim SH