Metastasis Flashcards
what is metastasis?
spread of malignant cells from the primary tumour to othe independent sites within the body
what is angiogenesis?
formation of blood supply (vascularisation) of tumour
occurs following transformation and initial growth of cells
when does the tumour need to form a blood supply and why
angiogenesis must occur to provide support for growth of the tumour mass (required for >1mm in diameter)
at tumour size >1mm, diffusion of nutrients and waste products become rate limiting for continued growth of tumour
how do tumours initiate angiogenesis
synthesis and secretion of pro-angiogenic factors (fibroblast growth factor FGF, vascular endothelial growth factor VEGF) by tumour cells and other non cancerous cell types around the cancer
how do cells become metastatic?
- Initial growth of cancerous cells and formation of a tumour, developing a vascular supply
- Factors produced by cancerous cells and surrounding non-cancerous cell types stimulate morphological changes in cells
- Phenotypic conversion and dedifferentiation of epithelial cells – indicative of carcinoma (epithelial derived cancer)
- Characterised by epithelial mesenchymal transition (EMT) enabling cells to migrate and invade the surrounding tissue; invasion of the vascular and lymphatic system → resulting in metastasis
who proposed the seed and soil hypothesis and what does it describe
Stephen Paget in 1889
distribution of metastasis is not by chance, instead metastases develop only when ‘seed’ and ‘soil’ are compatible
- ‘seeds’ - cancer cells with metastatic ability
- ‘soil’ - microenvironment
explain the bidirectional movement of metastasis and how it can impact recurrence
bi-directional movement of tumour cells between primary and distant tumour sites – metastases have the ability to re-seed the primary tumour site (due to a local environment within each site that is similar and conductive to tumour growth)
Following inital treatment, relapse can occur in the exact same location because the microenvironmetn dictates their location/ survival
what are the three principle factors of the seed and soil hypothesis?
- tumours are heterogenous - made up of cancer cells with subpopulations of host cells exibiting different properties
- metastasis is selective for cancer cells which demonstatre a combination of these particular properties - (in order to succeed in the secondary site)
- success of the resulting metastasis at the secondary site depends on its ability to interact with and utilise the ‘soil’, comprising multiple factors within the microenvironment
(host cells eg epithelial, fibrobalst, endothelial, leukocytes)
(properties eg angiogenic, invasive, metastatic, growth rate)
where does the epithelium sit and what is its major function?
epithelium sits on top of the connective tissure layer (stroma) (basal lamina separates the two
has a barrieer function to protect the underlying tissues and acts selectively to sort molecule between the lumen and underlying tissue
give five common sites of epithelial derived cancer
colon, breast, ovary, lung, prostate, pancrease
development of a cancerous growth within the epithelium leads to…
…disruption of tissue organisation and eventual invasion into the connective tissue layer
what are the stages of epithelial derive cancer from normal to carcinoma
normal epithelium
low grade intraepithelial neoplasia
high grade intraepithelial neoplasia
invasive carcinoma
what are the two key features of epithelial cells
they are polarised (apical and basal) and differentiated
what are the four types of junctions in epithelial tissues?
give examples for each
- tight junctions eg tight junction
- cell-cell anchoring junctions eg adherens junctions and desmosome
- channel forming junctions eg gap junctions
- cell-matrix anchoring junctions eg actin linked cell matrix junction and hemidesmosome
what is a tight junction?
give two components
a tight junction that seals gap between epithelial cells
zipper-like, restricts flow of molecules and water within the intracellular space, maintains an impermeable epithelial barrier
components, occludin, ZO-1
what is an adherens junction?
give two components
a cell-cell anchoring junction that connects actin filament bundles in one cell to that in the next cell
provides lateral adhesion between neighbouring epithelial cells - maintains actin contractile rings and epithelial polarity
components, e-cadherin, alpha actinin
what is a desmosome?
give two components
a cell-cell anchoring junction that connect intermediate filaments in one cell to those in the next cell
linked to intermediate fibres, functions to maintain adhesion and tissue integrity
components+ desmoplakin, cytokeratin
what is a gap junction?
a channel forming jucntion that allows the passage of small water soluble molecules from cell to cell
