重编程VEGF介导的细胞外基质变化通过自身隐性信号传递
Eibhlin Goggins1, Yelena Mironchik1, Samata Kakkad1
1Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Cancer biology & therapy
|June 30, 2023
概括
血管内皮生长因子 (VEGF) 在三阴性乳腺癌 (TNBC) 中改变了瘤微环境. 过度表达的VEGF减少了关键的细胞外基质蛋白,可能提供新的治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 血管内皮生长因子 (VEGF) 对血管生成和伤口愈合至关重要.
- 在三阴性乳腺癌 (TNBC) 中,VEGF通过改变细胞外基质 (ECM) 来促进侵袭和转移.
研究的目的:
- 为了调查TNBC中ECM的VEGF介导的修改.
- 为了确定参与TNBC中VEGF驱动的ECM重塑的分子参与者.
主要方法:
- 工程TNBC MDA-MB-231细胞过度表达VEGF.
- 具有特征的ECM组件 (原-1,纤维素,氨酸) 和矩阵修饰酶 (MMPs, uPAR, LOX, ADAMTS1).
- 分析了与癌症相关的纤维细胞 (CAF) 标志物 (α-SMA,FAP-α) 和使用癌症基因组图谱 (TCGA) 数据验证的结果.
主要成果:
- 在TNBC瘤中VEGF过度表达导致原蛋白1,纤维素和氨酸的减少.
- 观察到MMP1,UPAR和LOX的表达增加,MMP2和ADAMTS1的表达减少.
- VEGF影响了CAF标记物,并证明了对癌细胞系中酶表达的自身隐性作用.
结论:
- 在TNBC中,VEGF显著降低了关键的ECM蛋白质,与其在伤口愈合中的作用形成对比.
- 这些发现突显了VEGF在癌症进展中的多方面的作用,并建议治疗干预的ECM相关目标.
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
Mechanism of Angiogenesis
5.6K
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
5.6K
Autocrine Signaling
48.2K
Autocrine signaling is one of the many signaling mechanisms that function inside multicellular organisms to carry out intercellular communication. In this type of signaling mechanism, the same cell that secretes an extracellular signaling molecule also expresses the receptors to bind and respond to that signaling molecule.
Autocrine Signaling in Macrophages
Under normal physiological conditions, autocrine signaling is essential for maintaining homeostasis. This process is well characterized in...
Autocrine Signaling in Macrophages
Under normal physiological conditions, autocrine signaling is essential for maintaining homeostasis. This process is well characterized in...
48.2K
Intracellular Signaling Affects Focal Adhesions
2.7K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.7K
TGF - β Signaling Pathway
7.5K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.5K
The Extracellular Matrix
9.1K
Overview
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
9.1K


