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外泌体在前列腺癌转移中的作用。

Role of Exosomes in Prostate Cancer Metastasis.

机构信息

Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA.

Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA 30912, USA.

出版信息

Int J Mol Sci. 2021 Mar 29;22(7):3528. doi: 10.3390/ijms22073528.

Abstract

Prostate cancer remains a life-threatening disease among men worldwide. The majority of PCa-related mortality results from metastatic disease that is characterized by metastasis of prostate tumor cells to various distant organs, such as lung, liver, and bone. Bone metastasis is most common in prostate cancer with osteoblastic and osteolytic lesions. The precise mechanisms underlying PCa metastasis are still being delineated. Intercellular communication is a key feature underlying prostate cancer progression and metastasis. There exists local signaling between prostate cancer cells and cells within the primary tumor microenvironment (TME), in addition to long range signaling wherein tumor cells communicate with sites of future metastases to promote the formation of pre-metastatic niches (PMN) to augment the growth of disseminated tumor cells upon metastasis. Over the last decade, exosomes/ extracellular vesicles have been demonstrated to be involved in such signaling. Exosomes are nanosized extracellular vesicles (EVs), between 30 and 150 nm in thickness, that originate and are released from cells after multivesicular bodies (MVB) fuse with the plasma membrane. These vesicles consist of lipid bilayer membrane enclosing a cargo of biomolecules, including proteins, lipids, RNA, and DNA. Exosomes mediate intercellular communication by transferring their cargo to recipient cells to modulate target cellular functions. In this review, we discuss the contribution of exosomes/extracellular vesicles in prostate cancer progression, in pre-metastatic niche establishment, and in organ-specific metastases. In addition, we briefly discuss the clinical significance of exosomes as biomarkers and therapeutic agents.

摘要

在全球范围内,前列腺癌仍是一种危及男性生命的疾病。大多数与前列腺癌相关的死亡是由转移性疾病引起的,其特征是前列腺肿瘤细胞转移到各种远处器官,如肺、肝和骨。骨转移是前列腺癌中最常见的,伴有成骨和溶骨性病变。前列腺癌转移的确切机制仍在研究中。细胞间通讯是前列腺癌进展和转移的关键特征。除了长距离信号外,前列腺癌细胞与原发性肿瘤微环境(TME)内的细胞之间也存在局部信号,其中肿瘤细胞与未来转移部位进行通信,以促进形成预先转移的生态位(PMN),从而增强播散性肿瘤细胞转移后的生长。在过去的十年中,已经证明外泌体/细胞外囊泡参与了这种信号传递。外泌体是纳米大小的细胞外囊泡(EVs),厚度在 30 至 150nm 之间,起源于多泡体(MVB)与质膜融合后,并从细胞中释放出来。这些囊泡由包含生物分子(包括蛋白质、脂质、RNA 和 DNA)的货物的脂质双层膜组成。外泌体通过将其货物转移到受体细胞中来介导细胞间通讯,从而调节靶细胞功能。在这篇综述中,我们讨论了外泌体/细胞外囊泡在前列腺癌进展、预先转移生态位建立以及器官特异性转移中的作用。此外,我们还简要讨论了外泌体作为生物标志物和治疗剂的临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51e2/8036381/790d9f894952/ijms-22-03528-g001.jpg

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