Tumour Progression, Invasion and Metastasis Flashcards
Characteristics of Malignant Tumours:
What occurs during Progression?
→ How does this differ from Benign tumours?
What occurs during Invasion?
What occurs during Metastasis?
- Unlimited growth as long as an adequate blood supply is available
→ Benign tumours have limited growth - Migration of tumour cells into surrounding tissues, where they’re free to disseminate via the blood or lymph
- Spread of tumour cells from primary site to form a Secondary tumour
TUMOUR PROGRESSION:
What are the Molecular changes occurring here?
What is this process associated with?
→ What properties can vary between cells in a tumour?
- • Acquisition of specific mutations - by Carcinogens
• Clonal expansion - by Tumour promotors
• Genomic Instability
• Epigenetic changes - Cellular Heterogeneity - Selective pressures will determine the cell types in a tumour
→ Antigenicity, Growth rate, Response to hormones and cytotoxic drugs, Capacity for invasion and metastasis
TUMOUR INVASION:
What changes occur in the tumour during this stage?
——————
Neovascularisation:
What promotes Angiogenesis?
What are the main factors involved here?
→ How are they stored?
→ What are they released by?
Epithelial to Mesenchymal Transition (EMC):
What is this?
What is LOST during this?
Regulation of Proteolytic Activity:
What do most tissues have to regulate Proteinases?
→ How does this relate to Tumours?
- • Increased mechanical pressure due to rapid proliferation
• Hypoxia, leading to neovascularisation
• Epithelial to Mesenchymal Transition (EMC)
• Increased production of degrading enzymes by tumour and stromal cells
—————— - HYPOXIA
- VEGF, FGF2, TGF-β, HGF/SF
→ Bound to components of the ECM
→ Matrix Metalloproteinases (MMPs) - Angiogenesis Inhibitors e.g. Anti-VEGF like Bevacizumab, VEGF Receptor Inhibitors like Sorafenib
- Remodelling of cell-cell and cell-ECM interactions, leading to the detachment of Epithelial cells from each other and its basement membrane
- Epithelial shape, Cell polarity, Cytokeratin intermediate filament, and Epithelial junction protein (E-CADHERIN)
- Fibroblast-like shape, N-CADHERIN, Invasiveness, Vimentin intermediate filament, Mesenchymal gene expression, and Protease secretion
- TIMP (Tissue Inhibitor of Metalloproteinases), which inhibit Proteinases
→ Some tumours have ↓TIMP
METASTASIS:
Why is it a very inefficient process?
What is the Seed and Soil Hypothesis?
Compared to Tumour Invasion, what does Colonisation require to become a Secondary tumour?
- Tumour cells can easily extravasate most of the time, but find it difficult to become a Secondary tumour (Micro/Macrometastasis)
- There are Specific Adhesions between Tumour and Endothelial cells in the target organ, creating a favourable environment for colonisation
- Mesenchymal-Epithelial Transition (MET)
Liquid Biopsies:
What are they?
If a blood biopsy is taken, what can be detected?
What are CTCs? What does their presence in blood indicate?
- Sampling and analysis of Non-solid biological tissue (e.g. blood) for detection of molecular biomarkers
- Circulating Tumour Cells (CTCs), Cell free DNA etc.
- Tumour cells travelling in the blood - Indicates tumour growth and spread