微环境诱导的PTEN损失通过外体微RNA原体的大脑转移的增长
Lin Zhang1,2, Siyuan Zhang1,3, Jun Yao1
1Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center.
Nature
|October 20, 2015
概括
癌细胞通过逆向降低瘤抑制剂PTEN来适应大脑. 这一由星细胞微RNA介导的过程促进了大脑转移的生长,并提供了新的治疗点.
科学领域:
- 癌症学
- 细胞生物学
- 神经科学
背景情况:
- 转移需要瘤细胞适应外来微环境.
- 驱动器官特异性转移适应的机制在很大程度上是未知的.
- PTEN (酸酶和张素同类物) 是一个关键的瘤抑制剂.
研究的目的:
- 研究瘤细胞如何适应大脑的微环境.
- 阐明PTEN调节在大脑转移中的作用.
- 确定针对大脑转移的治疗策略.
主要方法:
- 在转移到不同器官的瘤细胞中对PTEN表达的比较分析.
- 通过天体细胞衍生的微RNA和外体细胞对PTEN的表观遗传调节的研究.
- 使用小鼠模型进行体内研究,以评估PTEN损失和治疗干预措施的影响.
- 化学激素 (CCL2) 分泌和骨髓细胞招募的分析.
主要成果:
- 瘤细胞特别在大脑中降低PTEN, 这是一个依赖于微环境的可逆过程.
- 通过外体传递的天体细胞衍生微RNA会在转移细胞中表观遗传抑制PTEN的表达.
- 损失PTEN增强了CCL2分泌,吸引了促进瘤细胞增殖和存活的骨髓细胞.
- 向星体外分泌或微RNA抑制了体内大脑转移.
结论:
- 在转移性瘤细胞中,PTEN表达具有高度可塑性,能够适应大脑的微环境.
- 通过微RNA外体进行的星细胞-瘤细胞通信驱动了适应性PTEN损失和大脑转移.
- 这项研究揭示了脑转移的新机制, 并提出了潜在的治疗点.
更多相关视频
12:13Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
7.3K
05:02Modeling Brain Metastasis Via Tail-Vein Injection of Inflammatory Breast Cancer Cells
Published on: February 4, 2021
3.9K
相关概念视频
The Tumor Microenvironment
8.1K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
8.1K
The Tumor Microenvironment
3.1K
3.1K
Metastasis
6.8K
Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
6.8K
MicroRNAs
24.7K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
24.7K
MicroRNAs
4.3K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
4.3K
