研究动态
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来自脂肪组织的间充质干细胞微泡:揭示它们对原发性卵巢癌细胞的影响及其治疗机会。

Mesenchymal Stem Cell Microvesicles from Adipose Tissue: Unraveling Their Impact on Primary Ovarian Cancer Cells and Their Therapeutic Opportunities.

发表日期:2023 Nov 01
作者: Agnieszka Szyposzynska, Aleksandra Bielawska-Pohl, Marek Murawski, Rafal Sozanski, Grzegorz Chodaczek, Aleksandra Klimczak
来源: Stem Cell Research & Therapy

摘要:

间充质干细胞(MSC)及其衍生物可以成为肿瘤学(包括卵巢癌治疗)中很有前途的工具。本研究旨在确定 HATMSC2-MV(源自脂肪组织来源的人类永生化间充质干细胞的微泡)对原发性卵巢癌细胞的命运和行为的影响。人原发性卵巢癌 (OvCa) 细胞从两个来源分离:卵巢癌术后组织和腹水。使用流式细胞术、实时RT-PCR和免疫荧光染色来表征细胞的表型。在 2D(增殖、迁移和细胞存活)和 3D(细胞存活)模型中分析 HATMSC2-MV 对原代细胞生物活性的影响。我们证明,内化到原发性卵巢癌细胞中的 HATMSC2-MV 会降低代谢活性并诱导癌细胞死亡,并导致肿瘤细胞的迁移活性降低。结果表明,HATMSC2-MV 的抗癌作用很可能是通过诱导细胞周期停滞和凋亡的分子(p21、肿瘤抑制因子 p53、执行器 caspase 3)和促凋亡调节因子(bad、BIM)的传递来实现的。 、Fas、FasL、p27、TRAIL-R1、TRAIL-R2),并且它们的存在已通过凋亡蛋白抗体阵列得到证实。在这项研究中,我们证明了 OvCa 细胞暴露于 HATMSC2-MVs 处理后抑制原代 OvCa 细胞生长和凋亡诱导的能力;然而,还需要进一步的研究来阐明它们的抗癌活性。
Mesenchymal stem cells (MSCs) and their derivatives can be promising tools in oncology including ovarian cancer treatment. This study aimed to determine the effect of HATMSC2-MVs (microvesicles derived from human immortalized mesenchymal stem cells of adipose tissue origin) on the fate and behavior of primary ovarian cancer cells. Human primary ovarian cancer (OvCa) cells were isolated from two sources: post-operative tissue of ovarian cancer and ascitic fluid. The phenotype of cells was characterized using flow cytometry, real-time RT-PCR, and immunofluorescence staining. The effect of HATMSC2-MVs on the biological activity of primary cells was analyzed in 2D (proliferation, migration, and cell survival) and 3D (cell survival) models. We demonstrated that HATMSC2-MVs internalized into primary ovarian cancer cells decrease the metabolic activity and induce the cancer cell death and are leading to decreased migratory activity of tumor cells. The results suggests that the anti-cancer effect of HATMSC2-MVs, with high probability, is contributed by the delivery of molecules that induce cell cycle arrest and apoptosis (p21, tumor suppressor p53, executor caspase 3) and proapoptotic regulators (bad, BIM, Fas, FasL, p27, TRAIL-R1, TRAIL-R2), and their presence has been confirmed by apoptotic protein antibody array. In this study, we demonstrate the ability to inhibit primary OvCa cells growth and apoptosis induction after exposure of OvCa cells on HATMSC2-MVs treatment; however, further studies are needed to clarify their anticancer activities.