瘤内皮细胞和癌细胞之间的交叉交互对于转移的启动非常重要
Victor Oginga Oria1, Joana Leitao Castro2, Jéssica de Pina Roque2
1Biotech Research and Innovation Center (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark. victor.oria@bric.ku.dk.
Cell communication and signaling : CCS
|October 16, 2025
概括
瘤内皮细胞 (TEC) 通过分泌PDGF-AA和PDGF-C等因素促进癌症转移,从而增强癌细胞的入侵和迁移. 瘤微环境中的这种交叉连接驱动了转移的启动.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 转移是癌症死亡的主要原因,涉及癌症和树皮细胞之间的复杂相互作用.
- 对于营养供应至关重要的内皮在转移启动中的作用仍然在很大程度上未被探索.
- 了解影响癌细胞的内皮衍生因素是破译转移机制的关键.
研究的目的:
- 研究正常内皮细胞 (NEC) 和瘤内皮细胞 (TEC) 在转移启动中的不同作用.
- 为了识别由TECs分泌的特定血管神经因子,调节癌细胞行为.
- 阐明在转移过程中涉及TEC癌细胞交叉通道的分子通路.
主要方法:
- 对NEC和TEC的扩散,迁移和血管生成潜力的比较分析.
- 来自NEC和TEC的条件介质对癌细胞化学反应,入侵和扩散的评估.
- 质谱测量用于识别TEC调节介质中的分泌因子.
- 使用重组蛋白和中和抗体进行体外功能研究.
- 在活体内, ортотоп性小鼠模型用于评估瘤生长和转移.
主要成果:
- 与NEC相比,TEC表现出更高的扩散,迁移和血管生成潜力.
- 经TEC调节的介质显著增强癌细胞化学反应,入侵和扩散.
- 与NEC相比,TECs促进了较快的癌细胞-癌细胞粘附.
- 确定PDGF-AA和PDGF-C是TEC分泌的关键因素,促进癌细胞入侵和化疗.
- 来自TEC的PDGF-C的中和抑制了癌细胞入侵和相关的信号通路.
- 同时注射TEC和癌细胞加速瘤生长和肝脏转移 in vivo.
结论:
- 癌细胞和TEC之间的交叉通话,由血管神经因子介导,驱动转移开始的关键步骤.
- TECs在促进瘤微环境中的转移级联中发挥着重要作用.
- 针对像PDGF-C这样的TEC衍生因素,可以作为对抗癌症转移的潜在治疗策略.
相关概念视频
Metastasis
6.4K
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...
6.4K
The Tumor Microenvironment
7.6K
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...
7.6K
Adaptive Mechanisms in Cancer Cells
6.9K
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,...
6.9K
Cancer Stem Cells and Tumor Maintenance
5.9K
Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
5.9K
Regulation of Angiogenesis and Blood Supply
3.3K
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...
3.3K
Cancer Cell Migration through Invadopodia
3.2K
Invadosome is a broad category of cell surface structures with proteolytic activity that degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
3.2K


