Tumour Vasculature structure and function Flashcards
What is normal tissue composed of?
Linear blood vessel lined by smooth layer of endothelial cells with pericytes. ECM of loose network of collagen and other fibres, containing few fibroblasts and macrophages. Lymph vessels also present.
What are the components of tumor structure?
Solid tumours composed of parenchyma and stroma (vasculo-connective tissue). Stroma is not neoplastic.
How is tumor tissue characterized?
Characterised by loss of normal tissue organisation of parenchyma and stroma, with rapid proliferation of stroma leading to imperfect blood vessel architecture.
What are the characteristics of tumor blood vessels?
Blood vessels are leaky and irregularly shaped with sac-like formations, dead ends, and highly activated endothelia. They exhibit inefficient blood flow and decreased vessel stability due to few pericytes.
What happens to lymph vessels in tumors?
Lack lymph vessels leads to inefficient removal of interstitial fluid and soluble proteins.
How does the ECM differ in tumor tissue compared to normal tissue?
Tumor tissue has a denser network of collagen fibres in ECM, making it more rigid than normal tissue.
What is the tumor microenvironment like?
It is hostile, characterized by O2 depletion and nutrient/energy deprivation, with significant variation in parameters over time and between individual tumors.
What are the functions of endothelial cells in normal vasculature?
Endothelial cells provide barrier functions, cell trafficking, perfusion and permeability, blood pressure regulation, and coagulation.
What role do pericytes play in normal vasculature?
Pericytes give stability to normal vasculature but are only loosely attached in tumors, causing instability.
What are the types of capillaries?
Non-fenestrated (continuous), fenestrated, and discontinuous capillaries, differing in structure and location.
What is the process of angiogenesis?
Angiogenesis involves sprouting, bridging, and intussusception, producing daughter vessels from mother vessels.
What is the angiogenic switch in tumors?
In cancer, the angiogenic switch is not turned off, resembling a ‘wound that never heals’ and is important for tumor progression.
What are the two main sources of blood vessels in tumors?
Vessels recruited from pre-existing vasculature and new vessels formed due to angiogenic response.
How do tumor blood vessels differ from normal blood vessels?
Tumor blood vessels are leaky, immature, multilayered, and undergo constant remodelling.
What is chronic hypoxia?
Chronic hypoxia occurs due to oxygen diffusion gradients, causing cells to stop replicating and become quiescent.
What is the role of HIF in hypoxia?
HIF accumulates in hypoxic cells, binds to hypoxia response elements (HREs), and recruits transcriptional co-activators to activate target genes.
What are tumor-associated macrophages (TAMs)?
TAMs are key components of the tumor microenvironment, attracted by hypoxia and producing growth factors that induce angiogenesis.
What are the main actions of the VEGF family?
VEGF family induces angiogenesis, increases permeability, causes vasodilation, and influences immune cell maturation.
What is the significance of VEGF-A?
VEGF-A primarily affects angiogenesis and vasculogenesis, with at least six isoforms differing in function.
What are the activators of angiogenic growth factors?
Activators include acidic and basic FGFs, PDGF, TGF-a, TGF-b, TNF-a, and angiogenin.
What are some inhibitors of angiogenesis?
Inhibitors include angiostatin, endostatin, platelet-factor 4, prolactin, thrombospondin, and TIMPs.
What methods are used to investigate hypoxia?
Methods include EF5 localization, CD-31 staining, and measuring acute and chronic hypoxia using short half-life drugs.
How do hypoxic cells respond to chemotherapy?
Hypoxic cells are more resistant to chemotherapy due to acidosis and upregulation of H ion pumps.
What are therapeutic targets related to hypoxia?
Targets include hypoxia-dependent drugs, HIF stability modulation, and VEGF inhibitors like Bevacizumab.
