Tumourigenesis Flashcards
Describe the differences between benign and malignant neoplasms
BENIGN
Often encapsulated
Well differentiated
(resembles normal tissue)
Low mitotic rate
(slow, progressive, expansive growth)
Non-invasive growth
(cohesive, expansile mass,
compressing adjacent tissue)
No metastasis
(localised at site of origin)
MALIGNANT
Non-encapsulated
Poorly differentiated
High mitotic rate
(rapid, erratic growth)
Invasive growth
(infiltrating & destroying
surrounding tissue)
Metastasising
(spread to secondary sites)
How does the loss of intracellular adhesion contribute to the invasive potential of malignant tumors?
disrupting the cohesive nature of cells within the tumour
allows malignant cells to detach from the primary tumour site and infiltrate surrounding tissues
outline the Steps of the invasive process
- Loss of intracellular adhesion
- Attachment to ECM
- Degradation of the ECM with Type IV collagenase and plasminogen activators
- migration through the BM
Explain the role of proteases, specifically MMPs and TIMPs, in the process of tissue invasion
proteases break down protein.
matrix metalloproteinases (MMPs)
secreted by both tumour and stromal cells
degrade the ECM, allowing tumour cells to penetrate basement membranes and migrate
tissue inhibitors of metalloproteinases (TIMPs)
regulate MMP activity
Describe the significance of the “seed and soil” hypothesis in understanding metastasis,
referencing Paget’s observations and the microenvironment concept.
seed = tumour cells
soil = microenvironment of the organ
How these facilitate metastasis:
microenvironment provides suitable conditions for their growth and survival, influenced my chemokines and GFs
- interplay between tumor cells and their surrounding tissue
According to Hanahan and Weinberg’s research, what are the parallel pathways of tumorigenesis?
how do factors like IGF and VEGF contribute to these pathways?
dysregulation of signalling cascades that drive proliferation, survival, and angiogenesis, ultimately contributing to tumor development and progression.
IGF – promotes prolif. and inhibits apoptosis. stimulates VEGF as an angiogenic factor. enhances tumor cell motility and invasiveness.
VEGF – regulator of angiogenesis, promoting the formation of new blood vessels.
How do chemokines function as homing factors for tumor cells, and what specific role does the CXCL12/CXCR4 interaction play in breast cancer metastasis?
directing their migration towards specific organs.
The CXCL12/CXCR4 interaction = role in breast cancer metastasis
CXCL12, produced by target organs, attracts CXCR4-expressing breast cancer cells, facilitating their colonisation and metastatic growth
Explain the process of angiogenesis in tumor growth, detailing the initiation, stimulation, and maturation phases as discussed in the workshop.
recruitment of endothelial cells from existing vessels,
stimulation of their proliferation,
migration towards the tumor,
and formation of new blood vessels.
essential for providing oxygen and nutrients to growing tumors beyond a certain size
involves the orchestrated action of various pro-angiogenic factors.
Discuss the role of VEGF and its receptors in tumor angiogenesis, highlighting the importance of VEGFR-2 and its association with tumor progression.
VEGF and its receptors, particularly VEGFR-2, play crucial roles in tumor angiogenesis. VEGF, secreted by tumor cells, binds to VEGFR-2 on endothelial cells, initiating signaling pathways that promote endothelial cell proliferation, migration, and tube formation. This interaction, as discussed in the workshop, is pivotal for the formation of new blood vessels within tumors to support their growth and metastasis.
What factors contribute to the activation of the angiogenic switch in tumors, and how does this switch lead to increased vascularization and tumor growth?
The angiogenic switch in tumors is triggered by factors such as hypoxia, growth factors, and oncogenes. This switch leads to a shift in the balance of pro-angiogenic and anti-angiogenic factors, resulting in increased vascularization and tumor progression. The process involves the upregulation of pro-angiogenic factors like VEGF and the downregulation of inhibitors of angiogenesis.
Describe the consequences of high VEGF levels in tumors, including their impact on interstitial pressure and the delivery of therapeutic agents.
High VEGF levels in tumors contribute to increased interstitial pressure, which can impede the delivery of therapeutic agents to the tumor microenvironment. This phenomenon, discussed in the workshop, poses a challenge for effective drug delivery and underscores the importance of targeting angiogenesis to improve treatment outcomes in cancer.
Provide an overview of anti-angiogenic therapies mentioned in the workshop, including the categories of inhibitors and their respective mechanisms of action.
Anti-angiogenic therapies target various components of the angiogenic process, including pro-angiogenic growth factors like VEGF, proteases involved in ECM remodeling, and cellular adhesion molecules. These therapies, categorized based on their mechanisms of action, aim to inhibit tumor angiogenesis and disrupt the tumor microenvironment to impede tumor growth and metastasis.
Differentiate between angiogenesis and vasculogenesis
Why is angiogenesis required for solid tumour growth
Explain the process of starting tumour angiogenesis and the role of hypoxia
