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推进前列腺癌研究:前列腺周围脂肪干细胞的探索

Advancing prostate cancer research: an exploration of periprostatic adipose stem cells.

作者信息

Sacca Paula Alejandra, Calvo Juan Carlos

机构信息

Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Vuelta de Obligado 2490, C1428ADN, Buenos Aires, Argentina.

出版信息

J Transl Med. 2025 Jul 14;23(1):794. doi: 10.1186/s12967-025-06734-6.

DOI:10.1186/s12967-025-06734-6
PMID:40660195
Abstract

Prostate cancer (PCa) is the most prevalent cancer among men, highlighting the urgent need for innovative treatment strategies. The periprostatic adipose tissue (PPAT) plays a crucial role in the PCa tumor microenvironment, with direct crosstalk between PPAT and PCa cells, particularly in advanced stages with extraprostatic extension-a feature linked to poor prognosis. Owing to their migratory capacity, adipose stem cells (ASCs) are promising in regenerative medicine and play a key role in tissue engineering and cancer research. These findings offer potential for novel approaches in targeted drug delivery and gene therapy for PCa. While ASCs within PPAT influence the tumor stroma, the mechanisms behind their interactions with PCa cells are not fully understood, with studies reporting both inhibitory and promoting effects on cancer progression. The adipose tissue secretome, including PPAT-ASC exosomal proteins, mediates communication between PPAT and PCa cells, with exosomal dysregulation observed in stage T3 PCa. This dysregulation implicates key cancer pathways such as integrin-mediated cell interactions, epithelialmesenchymal transition, and mRNA stability regulation. Although ASCs show promise as therapeutic carriers, their use is complicated by the need to prevent unwanted interactions with cancer cells. Moreover, environmental contaminants such as endocrine disruptors can alter ASC behavior, potentially influencing PCa development. This review synthesizes current knowledge on the multifaceted roles of ASCs and ASC-derived exosomes in PCa biology, their therapeutic applications, and the impact of environmental toxicants on their function and cancer-related outcomes. Further research into the underlying biological mechanisms is needed, highlighting the need for safe, targeted therapeutic approaches in PCa treatment.

摘要

前列腺癌(PCa)是男性中最常见的癌症,这凸显了对创新治疗策略的迫切需求。前列腺周围脂肪组织(PPAT)在PCa肿瘤微环境中起着关键作用,PPAT与PCa细胞之间存在直接的相互作用,特别是在伴有前列腺外扩展的晚期阶段——这一特征与预后不良有关。由于其迁移能力,脂肪干细胞(ASCs)在再生医学中具有广阔前景,并在组织工程和癌症研究中发挥关键作用。这些发现为PCa的靶向药物递送和基因治疗提供了新方法的潜力。虽然PPAT中的ASCs会影响肿瘤基质,但其与PCa细胞相互作用的机制尚未完全明确,研究报告显示其对癌症进展既有抑制作用也有促进作用。脂肪组织分泌组,包括PPAT-ASC外泌体蛋白,介导了PPAT与PCa细胞之间的通讯,在T3期PCa中观察到外泌体失调。这种失调涉及关键的癌症通路,如整合素介导的细胞相互作用、上皮-间质转化和mRNA稳定性调节。尽管ASCs有望作为治疗载体,但其应用因需要防止与癌细胞产生不必要的相互作用而变得复杂。此外,内分泌干扰物等环境污染物会改变ASC的行为,可能影响PCa的发展。本综述综合了关于ASCs和ASC衍生外泌体在PCa生物学中的多方面作用、它们的治疗应用以及环境毒物对其功能和癌症相关结果的影响的现有知识。需要对潜在的生物学机制进行进一步研究,这凸显了在PCa治疗中需要安全、靶向的治疗方法。

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本文引用的文献

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Applications of Gene Editing and Nanotechnology in Stem Cell-Based Therapies for Human Diseases.基因编辑与纳米技术在基于干细胞的人类疾病治疗中的应用。
Stem Cell Rev Rep. 2025 Feb 27. doi: 10.1007/s12015-025-10857-0.
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Spatial Genomics Identifies Heat Shock Proteins as Key Molecular Changes Associated to Adipose Periprostatic Space Invasion in Prostate Cancer.空间基因组学将热休克蛋白鉴定为与前列腺癌脂肪前列腺周围间隙浸润相关的关键分子变化。
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The Potential of Human Pulmonary Mesenchymal Stem Cells as Vectors for Radiosensitizing Metallic Nanoparticles: An In Vitro Study.
人肺间充质干细胞作为金属纳米颗粒放射增敏载体的潜力:一项体外研究
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Cancer-associated fibroblasts and prostate cancer stem cells: crosstalk mechanisms and implications for disease progression.癌症相关成纤维细胞与前列腺癌干细胞:相互作用机制及其对疾病进展的影响。
Front Cell Dev Biol. 2024 Jul 18;12:1412337. doi: 10.3389/fcell.2024.1412337. eCollection 2024.
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Potential Consequences of the Use of Adipose-Derived Stem Cells in the Treatment of Hepatocellular Carcinoma.脂肪来源干细胞在肝细胞癌治疗中的潜在后果。
Int J Mol Sci. 2024 Jul 17;25(14):7806. doi: 10.3390/ijms25147806.
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Tumoral periprostatic adipose tissue exovesicles-derived miR-20a-5p regulates prostate cancer cell proliferation and inflammation through the RORA gene.肿瘤前列腺周脂肪组织衍生的外泌体 miR-20a-5p 通过 RORA 基因调控前列腺癌细胞增殖和炎症。
J Transl Med. 2024 Jul 15;22(1):661. doi: 10.1186/s12967-024-05458-3.
7
Unveiling therapeutic potential: Adipose tissue-derived mesenchymal stem cells and their exosomes in the management of diabetes mellitus, wound healing, and chronic ulcers.揭示治疗潜力:脂肪组织来源的间充质干细胞及其外泌体在糖尿病、伤口愈合和慢性溃疡管理中的作用。
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Cancer-associated fibroblasts (CAFs) gene signatures predict outcomes in breast and prostate tumor patients.癌症相关成纤维细胞(CAFs)基因特征可预测乳腺癌和前列腺癌患者的预后。
J Transl Med. 2024 Jun 27;22(1):597. doi: 10.1186/s12967-024-05413-2.
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Hallmarks of cancer stemness.癌症干性的特征。
Cell Stem Cell. 2024 May 2;31(5):617-639. doi: 10.1016/j.stem.2024.04.004.
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Mesenchymal stem cell-derived exosomes for management of prostate cancer: An updated view.间充质干细胞衍生的外泌体在前列腺癌管理中的应用:最新观点。
Int Immunopharmacol. 2024 Jun 15;134:112171. doi: 10.1016/j.intimp.2024.112171. Epub 2024 May 2.