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癌症诊断与治疗中的细胞外囊泡

Extracellular vesicles in cancer diagnostics and therapeutics.

作者信息

Shehzad Adeeb, Islam Salman Ul, Shahzad Raheem, Khan Salman, Lee Young Sup

机构信息

Department of Biomedical Sciences, School of Mechanical and Manufacturing Engineering (SMME), National University of Sciences and Technology (NUST), H-12, Islamabad, Pakistan.

School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Korea.

出版信息

Pharmacol Ther. 2021 Jul;223:107806. doi: 10.1016/j.pharmthera.2021.107806. Epub 2021 Jan 17.

Abstract

Cancer promotion, development, and malignant transformation is greatly influenced by cell-to-cell interactions in a complex tissue microenvironment. Cancer and stromal cells secrete soluble factors, as well as deport membrane-encapsulated structures, which actively contribute and mediate cell-to-cell interaction within a tumor microenvironment (TME). These membrane structures are recognized as extracellular vesicles (EVs), which include exosomes and microvesicles. They can carry and transport regulatory molecules such as oncogenic proteins, coding and non-coding RNAs, DNA, and lipids between neighboring cells and to distant sites. EVs mediate crucial pathophysiological effects such as the formation of premetastatic niches and the progression of malignancies. There is compelling evidence that cancer cells exhibit a significant amount of EVs, which can be released into the surrounding body fluids, compared with nonmalignant cells. EVs therefore have the potential to be used as disease indicator for the diagnosis and prognosis of cancers, as well as for facilitating research into the underlying mechanism and biomolecular basis of these diseases. Because of their ability to transport substances, followed by their distinct immunogenicity and biocompatibility, EVs have been used to carry therapeutically-active molecules such as RNAs, proteins, short and long peptides, and various forms of drugs. In this paper, we summarize new advancement in the biogenesis and physiological roles of EVs, and underpin their functional impacts in the process of cancer growth and metastasis. We further highlight the therapeutic roles of EVs in the treatment, prevention, and diagnosis of human malignancies.

摘要

在复杂的组织微环境中,细胞间相互作用对癌症的促进、发展及恶性转化有着极大影响。癌症细胞和基质细胞会分泌可溶性因子,还会释放膜包裹结构,这些对肿瘤微环境(TME)中的细胞间相互作用起到积极作用并介导其发生。这些膜结构被认为是细胞外囊泡(EVs),包括外泌体和微囊泡。它们能够在相邻细胞之间以及向远处位点携带和运输调控分子,如致癌蛋白、编码和非编码RNA、DNA及脂质。细胞外囊泡介导关键的病理生理效应,如前转移小生境的形成和恶性肿瘤的进展。有确凿证据表明,与非恶性细胞相比,癌细胞会大量释放细胞外囊泡,这些囊泡可释放到周围体液中。因此,细胞外囊泡有潜力用作癌症诊断和预后的疾病指标,也有助于对这些疾病的潜在机制和生物分子基础进行研究。由于其运输物质的能力,以及独特的免疫原性和生物相容性,细胞外囊泡已被用于携带具有治疗活性的分子,如RNA、蛋白质、长短肽及各种形式的药物。在本文中,我们总结了细胞外囊泡生物发生和生理作用的新进展,并强调了它们在癌症生长和转移过程中的功能影响。我们还进一步突出了细胞外囊泡在人类恶性肿瘤治疗、预防和诊断中的治疗作用。

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