Decorin suppresses tumor lymphangiogenesis: A mechanism to curtail cancer progression
These videos have been matched automatically. Contact us if they are not relevant.
These videos have been matched automatically. Contact us if they are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.Decorin, a proteoglycan, inhibits breast cancer growth by blocking lymphatic vessel development. It targets vascular endothelial growth factor receptor 3 (VEGFR3), offering potential as an anti-cancer therapeutic agent.
Area Of Science
- Oncology
- Molecular Biology
- Biochemistry
Background
- Tumor growth involves complex interactions between cancer cells and the tumor stroma.
- Soluble bioactive molecules like proteoglycans modulate these tumor-host interactions.
- Decorin, a small leucine-rich proteoglycan, influences cancer progression by interacting with receptor tyrosine kinases (RTKs).
Purpose Of The Study
- To investigate the effect of systemically delivered decorin on tumor-associated gene expression, specifically focusing on lymphatic vessel development.
- To elucidate the mechanism by which decorin affects lymphangiogenesis and its potential as a therapeutic agent for breast cancer.
Main Methods
- Deep RNA sequencing (RNAseq) was used for unbiased transcriptomic analysis in mice with breast carcinoma allografts.
- In vitro studies utilized a 3D model of lymphangiogenesis to assess decorin's effect on lymphatic vessel sprouting.
- Mechanistic studies involved investigating decorin's interaction with vascular endothelial growth factor receptor 3 (VEGFR3) and decorin-evoked autophagy.
Main Results
- Decorin down-regulated genes involved in lymphatic vessel (LV) development, suppressing key markers like Lyve1 and Podoplanin at mRNA and protein levels.
- Systemic decorin administration significantly reduced tumor lymphatic vessel density.
- Soluble decorin inhibited LV sprouting ex vivo and this effect was dependent on its interaction with VEGFR3.
- Decorin induced the degradation of Lyve1 via autophagy.
Conclusions
- Decorin exhibits significant antilymphangiogenic activity.
- Decorin's interaction with VEGFR3 is crucial for blocking lymphangiogenesis.
- Decorin presents a potential therapeutic strategy for inhibiting breast cancer growth and metastasis by targeting lymphatic vessel formation.
These videos have been matched automatically. Contact us if they are not relevant.
These videos have been matched automatically. Contact us if they are not relevant.
Related Concept Videos
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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...
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...
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...