Kate Angel 2 Flashcards
What is colonisation in cancer metastasis?
If the micrometastasis (formed from the cell entering the parenchyma)develops into a clinically detectable masses known as macrometastasis
What are the methods of detecting micrometastasis in tissues?
Labelled antibodies can be used to detect cancer cells by binding to unique molecules on the cell this method can detect a single cell metastastasis
Trained pathologists may also use cell morphology to detect clusters of cancer cells
Why is colonisation the most challenging step in the metastasis cascade?
The new tissue environment may not provide the cell with familiar/suitable for survival and growth factors
The tumour cell may become dormant
Some cells may be able to survive but very few of these are able to fully colonize the tissue
How can colonising ability of a cancer be modelled as evolution?
A heterogeneous primary tumour seeds heterogeneous micrometastasis throughout the body
The primary tumour may then be removed and one of the micrometastasis will acquire the ability to colonize leading the to the generation of a new metastatic cascade with cancer cells that are able to rapidly colonize
How can dormant micrometastases represent a threat?
Dormant micrometastases are when disseminated cancer cells remain dormant, have their proliferation balanced by cell death or have their growth controlled by the immune system
Some of these can remain viable for long period of times and as they are frequently undetected they can later acquire the capacity to colonize through unknown mechanisms can result in disease years after the patient has been declared cancer free
What are the cellular changes associated with an EMT?
Expression of E-cadherin and cytokeratin is repressed and expression of vimentin is induced
Cells which have undergone EMT start to make the extracellular matrix component fibronectin
Expression of the fibroblastic marker N-cadherin is upregulated with increased resistance to apoptosis
What does the EMT represent in cancer?
The first step in metastasis is the acquisition of local invasiveness achieved by detaching from the epithelial sheets undergo EMT
What is cytokeratin?
It is a component of the intermediate filaments in epithelial cells which help to anchor the demisomes and hemidemisomes in place
What is the molecule that plays the dominant role in influencing epithelial vs mesenchymal cell phenotypes?
E-cadherin
What are cadherins?
Transmembrane proteins which regulate epithelial cell behaviours and form dimers between E-cadherin on adjacent cells to hold them together on the cytosolic side these proteins are connected to cytoskeletal elements via anchor proteins
How does E-cadherin expression change within different regions of tumours?
It is strongly expressed by the cells at the core of the primary tumour but repressed at the invasive edge of the tumour
How does the loss of E-cadherin during an EMT influence gene regulation?
Loss of E-cadherin destroys cell junctions which frees beta-cadherin for action as a transcription factor
This increases expression of N-cadherin which can bind to other N-cadherin molecules on adjacent cells these are most commonly expressed on stromal cells allowing the cancer cells to associate with them facilitating invasion
What evidence suggests that E-cadherin expression impeded invasiveness of cancer?
It is repressed in EMT and is correlated to increased motility of cancer cells
The CDH1 gene which specifies E-cadherin is suppressed by transcriptional repressors in many types of human invasive carcinomas
Re-expression of E-cadherin in tumour cells in vitro impairs their invasive behaviour
