8- angiogenesis and metastasis Flashcards
What is metastasis, and how does it contribute to cancer progression?
Metastasis is the spread of tumor cells from a primary site to establish secondary tumors. As tumors progress, cells invade surrounding tissues, enter the bloodstream, and form secondary areas of proliferation, impacting health significantly.
Explain the process of loss of attachment in metastasis
Loss of attachment involves mutations in cell adhesion molecules like E-cadherin, causing a loss of attachment between tumor cells and their neighbors. This allows tumor cells to break away, release proteases to digest the extracellular matrix, and invade surrounding tissues
How do cancer cells escape the extracellular matrix (ECM) and basement membrane during metastasis?
Cancer cells escape the ECM and basement membrane by secreting proteases that digest these structures. This facilitates invasion into blood capillaries, enabling the cells to migrate to new locations.
What are the steps involved in the metastatic process, particularly during intravasation and extravasation?
Intravasation involves cancer cells entering the bloodstream, while extravasation is when these cells leave the bloodstream, attaching to endothelial cells and entering other tissues or organs.
How does angiogenesis contribute to tumor growth, and what role does VEGF play?
Tumors require angiogenesis, the formation of new blood vessels, to grow beyond a certain size. Vascular Endothelial Growth Factor (VEGF) is a critical regulator of angiogenesis, facilitating improved blood supply to tumor cells.
Describe the process of sprouting angiogenesis and the angiogenic switch.
Sprouting angiogenesis involves the release of activators like VEGF by tumor cells. Endothelial cells, including tip cells and stalk cells, migrate toward the source, leading to the formation of new blood vessels. The angiogenic switch is the balance shift toward pro-angiogenic factors due to hypoxia.
What are the characteristics of leaky vessels in newly formed tumor vasculature?
Newly formed tumor vessels are often leaky, with loose endothelial cell contacts, loose association with pericytes, and abnormal basement membrane associations. This allows tumor cells to enter the bloodstream, facilitating metastasis.
What is anti-angiogenic therapy, and how does it aim to target tumor blood vessels?
Anti-angiogenic therapy involves drugs that target cancer blood vessel growth. These drugs may block VEGF binding to VEGFR or inhibit tyrosine kinases to stop VEGFR signaling, aiming to halt vessel growth
What are the key concepts related to metastasis?
Metastasis is the spread of tumor cells from a primary site to set up secondary tumors. It is a multistep process, involving uncontrolled growth, angiogenesis, invasion, intravasation, survival in circulation, extravasation, and dormancy/secondary tumor growth. Host-tumor interactions and the tumor microenvironment are critical.
