Angiogenesis and Cancer Overview

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Questions and Answers

What is the maximum distance cells can be from a blood vessel to receive adequate oxygen and nutrients?

50-100 µm

100-200 µm (correct)

300-400 µm

200-300 µm

What triggers the accumulation of HIF-1a in tumor cells?

Nutrient deprivation

Increased blood flow

Hypoxia (correct)

Excess oxygen

What is the primary function of VEGF in angiogenesis?

To induce apoptosis in tumor cells

To enhance blood vessel leakage

To promote endothelial cell growth (correct)

To trigger necrosis in hypoxic areas

What do tip cells form during angiogenic sprouting?

Lumen within the sprout Signup and view all the answers

How does the vascular structure in cancer differ from normal angiogenesis?

It is more disorganized Signup and view all the answers

What is the role of VHL in relation to HIF-1a?

It binds to and degrades HIF-1a Signup and view all the answers

What happens when two tip cells meet during angiogenesis?

They fuse to create a lumen Signup and view all the answers

Which of the following characterizes cancer-induced vasculature?

Tortuous and leaky structure Signup and view all the answers

What is one reason why cancer cells induce angiogenesis?

Hypoxia caused by rapid cell growth Signup and view all the answers

Which oncogene is mentioned as an activator of VEGF?

Ras Signup and view all the answers

How does the loss of p53 affect angiogenesis?

It reduces the inhibition of angiogenesis. Signup and view all the answers

What term describes the formation of vessel-like channels by tumor cells?

Vascular mimicry Signup and view all the answers

What role do endothelial progenitor cells from the bone marrow play in angiogenesis?

They form new blood vessels in tumors. Signup and view all the answers

What percentage of tumor endothelial cells are derived from circulating endothelial progenitor cells?

40% Signup and view all the answers

Which statement correctly describes the angio-genic switch in cancer?

It leads to an increase in angiogenic factors. Signup and view all the answers

What major mechanism is involved in vasculogenesis?

Differentiation of endothelial progenitor cells Signup and view all the answers

What does the 'seed' represent in the seed and soil hypothesis?

Cancer Cells Signup and view all the answers

Which step in the metastatic cascade involves the cell acquiring malignant characteristics?

Developing a Metastatic Cell Signup and view all the answers

Which common site is most frequently associated with breast cancer metastasis?

Bone Signup and view all the answers

Which process describes the transition of epithelial cells to a more mobile mesenchymal phenotype during metastasis?

Epithelial to Mesenchymal Transition (EMT) Signup and view all the answers

What does the term 'soil' refer to in the context of the seed and soil hypothesis?

Secondary organs and environment Signup and view all the answers

What is the fifth step in the metastatic cascade?

Cellular Arrest, Vascular Adhesion, and Extravasation Signup and view all the answers

Which cancers are primarily known to metastasize to the brain?

Melanoma, Breast, and Lung Signup and view all the answers

Which step follows 'Intravasation' in the metastatic cascade?

Dissemination and Transport Signup and view all the answers

What is the role of VEGF in angiogenesis?

It is a primary activator for the process. Signup and view all the answers

Which of the following is considered an endogenous inhibitor of angiogenesis?

Angiostatin Signup and view all the answers

Angiostatin functions by binding to which type of cell?

Endothelial cells Signup and view all the answers

What is the significance of VEGFA and VEGFR2 in the angiogenic pathway?

They are the main signaling pathway for angiogenesis. Signup and view all the answers

How does an increase in angiogenic activators affect angiogenesis?

It promotes the angiogenic switch to 'on'. Signup and view all the answers

What molecule is cleaved from plasminogen to release an angiogenic inhibitor?

Angiostatin Signup and view all the answers

Which factors are described as promoting angiogenesis?

VEGF and other activators Signup and view all the answers

What is the relationship between VEGF and tumor cells?

Tumor cells are a source of VEGFA. Signup and view all the answers

What is the key activator for angiogenesis in tumors?

VEGF Signup and view all the answers

Which hypothesis describes the behavior of metastasis in cancer?

Seed and Soil Hypothesis Signup and view all the answers

What process includes recruiting cells from the bone marrow to form new blood vessels?

Vasculogenesis Signup and view all the answers

Which of the following is NOT a mechanism associated with tumor angiogenesis?

Metastatic Cascade Signup and view all the answers

Which of the following best defines metastasis?

The spread of cancer cells to distant sites in the body Signup and view all the answers

What term is used to describe the complex process that enables successful colonization and growth of metastatic tumors?

Metastatic Cascade Signup and view all the answers

What is the major cause of clinical mortality in cancer patients?

Metastasis Signup and view all the answers

Who proposed the seed and soil hypothesis of metastasis?

Stephen Paget Signup and view all the answers

Study Notes

Angiogenesis

Angiogenesis is a balance of angiogenic inhibitors and activators.
An increase in activators, such as VEGF, promotes the "angiogenic switch" to "on".
VEGF (Vascular Endothelial Growth Factor) is the main activator of angiogenesis.
VEGF binds to receptors on endothelial cells, triggering migration and proliferation.
The main signaling pathway for angiogenesis involves VEGFA and VEGFR2.
VEGFA is secreted by tumor cells.
Angiostatin is an endogenous inhibitor of angiogenesis, which is released when plasminogen is cleaved.
Angiostatin binds to receptors on endothelial cells, preventing angiogenesis.

Angiogenesis in Cancer

Cancer cells require access to oxygen and nutrients, which are supplied by blood vessels.
Cells must be within 100-200 µm of a blood vessel to receive sufficient oxygen and nutrients.
Tumor cells in the core, which lack access to oxygen and nutrients, die by necrosis.
Hypoxia (low oxygen) stimulates tumor cells to produce VEGF, which promotes angiogenesis.
The VHL (von Hippel Lindau) protein degrades HIF1a (hypoxia-inducible factor) when oxygen levels are normal.
Under hypoxia, HIF1a accumulates, inducing VEGF expression.

Process of Angiogenic Sprouting

Binding of VEGF induces the formation of an endothelial cell "tip cell" at the forefront of a sprout.
Proliferating stalk cells located behind the tip cell extend the sprouting vessel.
The growing sprout follows a VEGF gradient.
When two tip cells meet, they fuse, creating a lumen that allows blood to flow.

Vasculature in Cancer

Vasculature in cancer is abnormal compared to normal angiogenesis.
It is characterized by leakiness, tortuosity, disorganization, inadequate flow, and direct entry for cancer cells into the circulation.

How Do Cancer Cells Induce Angiogenesis?

Cancer cells can induce angiogenesis by:
- Creating areas of hypoxia due to rapid growth.
- Activating oncogenes, including EGFR, Src, and Ras, which all activate VEGF.
- Loss of tumor suppressor genes:
  - Loss of VHL increases HIF1a activity.
  - Loss of p53 results in the absence of Thrombospondin, an angiogenesis inhibitor.

Other Angiogenic Mechanisms

Vascular mimicry:
- Tumor cells imitate blood vessels, forming vessel-like channels.
- Cancer cells also can grow through a leaky matrix of tumor bed.
Vasculogenesis:
- Recruitment of endothelial progenitor cells from bone marrow.
- These cells differentiate and contribute to the tumor neovasculature.
- 40% of tumor endothelial cells are from circulating endothelial progenitor cells derived from bone marrow.

Metastasis

Metastasis is the spread of cancer cells from the primary tumor to other parts of the body.
The seed and soil hypothesis explains metastasis, stating that certain cancers favor specific organs for metastasis.
The metastatic cascade outlines the steps involved in successful metastasis.

The Metastatic Cascade

The metastatic cascade consists of the following steps:
- Developing a metastatic cell.
- Motility and invasion.
- Intravasation (entering the bloodstream).
- Dissemination and transport.
- Cellular arrest, vascular adhesion, and extravasation (exiting the bloodstream).
- Colonization.

Developing a Metastatic Cell

The cell acquires more malignant oncogene activation, altering its behavior.

Motility and Invasion

The cell acquires the ability to break down the basement membrane (e.g., collagen) and migrate.
This involves epithelial-to-mesenchymal transition (EMT).

Metastasis Hallmarks

Metastasis is influenced by both tumor cell and tissue-specific factors.

Conclusions

Tumors utilize angiogenesis to recruit their own blood supply.
VEGF is pivotal in activating angiogenesis.
Other angiogenic mechanisms include vascular mimicry and vasculogenesis.
Metastasis is a major cause of mortality in cancer patients.
The seed and soil hypothesis outlines the organ-specific nature of metastasis.
The metastatic cascade clarifies the sequential steps involved in successful metastasis.

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Description

This quiz explores the concept of angiogenesis, its regulation by factors like VEGF, and its critical role in cancer proliferation. Understand how the balance between angiogenic activators and inhibitors affects tumor growth and the supply of oxygen and nutrients. Delve into the mechanisms that allow tumor cells to thrive despite limited access to blood vessels.