膀癌细胞和纤维细胞之间的依赖HGF的正反循环介导淋巴血管生成和淋巴转移
Yuting Li1, Hanhao Zheng2,3, Yuming Luo4
1Department of Oncology, Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, P. R. China.
Cancer communications (London, England)
|July 24, 2023
概括
这项研究揭示了LINC00665如何通过激活癌症相关纤维细胞 (CAF) 来促进膀癌 (BCa) 淋巴结转移. 针对LINC00665提供了转移性BCa的潜在治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 与癌症相关的纤维细胞 (CAFs) 通过与癌细胞的相互作用驱动瘤的进展.
- 瘤衍生的细胞外囊泡 (EVs) 介导癌症和 stromal 细胞之间的通信,促进转移.
- 在膀癌 (BCa) 淋巴结 (LN) 转移中,EV介导CAF激活的机制在很大程度上仍未被探索.
研究的目的:
- 研究瘤衍生的EVs在调节CAFs表型中的作用.
- 阐明CAFs表型影响BCa LN转移的分子机制.
- 为了确定驱动BCa LN转移的EV-CAF交叉语音中的关键介质.
主要方法:
- 高通量测序以识别与CAF相关的长非编码RNA (lncRNAs).
- 在体外和体内测试以评估LINC00665介导的EV对纤维细胞到CAF过渡的功能作用.
- 染色体测定,细胞因子分析和患者衍生异种移植 (PDX) 模型,以探索潜在的机制.
主要成果:
- CAFs富含BCa,与淋巴血管生成和LN转移相关.
- LINC00665是一种新型的lncRNA,它调解了CAF在BCa中的透,并与LN转移和不良预后有关.
- LINC00665上调RAB27B,促进EV分泌和CAF表型,建立RAB27B-HGF-c-Myc反循环,增强BCa淋巴血管生成和LN转移.
结论:
- LINC00665通过涉及CAF的RAB27B-HGF-c-Myc反循环驱动BCa LN转移.
- 阻断EV传播的LINC00665或HGF可以抑制BCa淋巴血管生成.
- LINC00665代表了LN转移性BCa.的潜在治疗标.
关键词:
与癌症相关的纤维细胞.在HGF的基础上.膀癌:膀癌是一种癌症.细胞外囊泡中的细胞外囊泡.长非编码RNA是什么意思淋巴结转移是淋巴结的转移.淋巴血管生成 (Lymphangiogenesis) 是一种导致淋巴血管发生的过程.积极的反循环是一个循环.更多相关视频
09:52A Mimic of the Tumor Microenvironment: A Simple Method for Generating Enriched Cell Populations and Investigating Intercellular Communication
Published on: September 20, 2016
10.4K
15:43Experimental Generation of Carcinoma-Associated Fibroblasts CAFs from Human Mammary Fibroblasts
Published on: October 25, 2011
23.5K
相关概念视频
Regulation of Angiogenesis and Blood Supply
2.6K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
The Tumor Microenvironment
6.7K
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...
6.7K
Metastasis
5.6K
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...
5.6K
Mitogens and the Cell Cycle
6.6K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.6K
Adaptive Mechanisms in Cancer Cells
5.8K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.8K
Tumor Progression
6.4K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.4K
