Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen 518060, China.
Department of Central Laboratory, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People's Hospital of Shenzhen, Shenzhen 518172, China.
Biomolecules. 2024 Sep 2;14(9):1099. doi: 10.3390/biom14091099.
Ovarian cancer remains a leading cause of death among gynecological cancers, largely due to its propensity for peritoneal metastasis and the development of drug resistance. This review concentrates on the molecular underpinnings of these two critical challenges. We delve into the role of exosomes, the nano-sized vesicles integral to cellular communication, in orchestrating the complex interactions within the tumor microenvironment that facilitate metastatic spread and thwart therapeutic efforts. Specifically, we explore how exosomes drive peritoneal metastasis by promoting epithelial-mesenchymal transition in peritoneal mesothelial cells, altering the extracellular matrix, and supporting angiogenesis, which collectively enable the dissemination of cancer cells across the peritoneal cavity. Furthermore, we dissect the mechanisms by which exosomes contribute to the emergence of drug resistance, including the sequestration and expulsion of chemotherapeutic agents, the horizontal transfer of drug resistance genes, and the modulation of critical DNA repair and apoptotic pathways. By shedding light on these exosome-mediated processes, we underscore the potential of exosomal pathways as novel therapeutic targets, offering hope for more effective interventions against ovarian cancer's relentless progression.
卵巢癌仍然是妇科癌症死亡的主要原因，主要是因为它倾向于腹膜转移和耐药性的发展。本综述集中讨论了这两个关键挑战的分子基础。我们深入研究了外泌体的作用，外泌体是细胞通讯中不可或缺的纳米大小囊泡，在协调肿瘤微环境中的复杂相互作用中发挥作用，促进转移扩散并破坏治疗效果。具体来说，我们探讨了外泌体如何通过促进腹膜间皮细胞中的上皮-间充质转化、改变细胞外基质和支持血管生成来驱动腹膜转移，这些共同使癌细胞能够在腹膜腔内扩散。此外，我们剖析了外泌体导致耐药性出现的机制，包括化疗药物的隔离和排出、耐药基因的水平转移以及关键的 DNA 修复和凋亡途径的调节。通过阐明这些外泌体介导的过程，我们强调了外泌体途径作为新的治疗靶点的潜力，为更有效地干预卵巢癌的无情进展带来了希望。
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