Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
27 Cards in this Set
- Front
- Back
|
Which neoplasms rarely metastasize even when malignant?
|
-Gliomas
-Basal cell carcinomas of skin |
|
|
Name two types of the extracellular matrix.
|
-Interstitial matrix
-Basement membrane |
|
|
What is the extracellular matrix made up of? what two organizations can it form?
|
-Fibrous structural proteins - Collagen and elastins
-Adhesive glycoproteins -Proteoglycans and hyaluronic acid -interstitial matrix and basement membrane |
|
|
What are the functions of the extracellular matrix?
|
-Matrix proteins secrete water to soft tissue and minerals to hard tissues
-Resivoirs of growth factors -Provides a substrate for cells to adhere, migrate and proliferate -Important in cell-cell interactions -Its synthesis and degradation is important in morphogenesis, wound healing and chronic fibrotic processes |
|
|
What is the EMT process?
|
-The epitheleal mesenchymal transition is a process that ocurs when epithelial cells lose cell-cell polarity and cell-adhesion and gain migratory and invasive properties, becoming mesenchymal stem cells.
|
|
|
Name a protein that is not expressed in order to enable EMT?
|
-epithelial cadherin (E-cadherin) is not expressed
|
|
|
What is the Function of Zinc finger protein SNAI1?
|
-It downregulates the expression of ectodermal genes
-It downregulates E-cadherin production which induces EMT, making it an important transcription factor in cancer |
|
|
What is the function of ZInc function protein SNAI2?
|
-Also known as SLUG, it is a transcription factor that represses E-cadherin production and also has anti-apoptotic properties
|
|
|
Which factors repress E-cadherin transcription directly?
|
-Snail, Slug, ZEB1, ZEB2, E47 and KLf8
|
|
|
Which factors indirectly suppress E-cadherin transcription ?
|
-TWIST
-FOXC2 -SIX1 -Goosecoid |
|
|
What must be broken down and remodelled for a tumour to become invasive?
|
- The extracellular matrix (basement membrane)
|
|
|
What is the function or fibronectin? How is it involved in the EMT process?
|
- Fibronectin is a like a structural mesh that is involved in cell adhesion and controls growth,migration and differentiation via cell-ECM binding.
-Many cancers show a decreased expression of fibronectin, Increased degradation of it or a decrease in fibronectin specific integrins |
|
|
WHy is the role of fibronectin in lung cancer different?
|
-In lung carcinoma fibronectin expression is increased and this may give it radioresistance and resistance to chemotherapy drugs.
|
|
|
What is the function of the laminins and how are they involved in the EMT process?
|
-Laminins are a family of glycoproteins that bind cells to the basement membrane, normal epthileal cells express intergrin/immunoglobulin laminin receptors on one side (polar) that organise them into a regular shape.
-Cancers over express laminin receptors all over the cell so they become non polar. |
|
|
What is the function os Osteonectin? How does this play an important role in cancer?
|
-Osteonectin is a glycoprotein that is important in bone mineralization, cell-matrix interactions and collagen binding. It induces the expression of MMPS-1,3,9 which all degrade basement membranes. It also contributes to angiogenesis, proliferation and migration.
-It is often over expressed in many cancers and melanoma cells that did not express it could not generate any more tumours in mice. |
|
|
What is the function of calcium dependent proteins? How are they involved in the morphology of Cancer
|
-Cadherins bind cells together by the membrane forming zonula adherens and stronger desmosomes. They are linhked to the cell via the beta cantenin which is linbked to the alpha cantenin on the intracellular cytoskeleton
-E-cadherins bind epitheleal cells and relay signals between the cells in order to control growth. In some cancers it is down regulated causing cellular detachment and irregularity , Or the catenin can be underexpressed rendering E-cadherin useless |
|
|
WHat is the normal function of the integrins? How is this changed in cancer?
|
-The integrins bind the cell to variosu components of the extracellular matrix such as collagen, fibronectin and laminin
-Tumours cells may show an increase in the amount of integrins and produce integrins that are not poresent in normal tissue. Certain integrins increase the metastatic properties of cacner when expressed. |
|
|
What is the full name of HSGAG? How is it involved in cancer metastasis?
|
-Heparan-sulphate glycosaminoglycans
-Act to activate P-selectins , Binding pplatelet lets to the tumour cell surface or endothelialium of blood vessels. -Also acts as a co-receptor for integrin binding to the basement membrane, migrating cells. -When cleaved by heparanase It releases growth factors |
|
|
What is the role of P-selectin in normal cellular function? How is it involved in cancer?
|
-P-selectin is found in the endothelial cells and platlets. It is expressed on their surface when these cells are activated by things like Inflammation. IT binds to ligands found in neutrophils, eosinophils, lymphocytes and monocytes recruiting them to sites of inflammation. (scab will want this movement for immune system.)
- The ligand HSGAG binds to P selectins in order to move the cell towards blood stream, then coat it in platelets to avoid apopotosis by N kill cells. It then helps bind a free tumour cell to a secondary tumour site by attaching to P-selectins on the endothelium. -P-selectins are therapeutic targets as using heparin to reduce heparnase activity can induce severe bleeding. |
|
|
How are platelets a potential therapeutic target in the treatment of cancer?
|
- Reduction in the amount of circulating platelets could reduce cancer metastasis as shown in mice. This is due to removing their "invisibility cloak" of platelets
|
|
|
What is a matrix metalloproteinase? What is its function?
|
-Is a zinc-dependent endoproteinase
-Important in tissue remodelling. Involved in degrading the extracellular matrix, cleave cell surface receptors, release apoptotic ligands and cause chemokine/cytokine inactivation |
|
|
Which MMPs are important in cancer metastasis? Why?
|
-MMP-2 and MMP-9 are important in cancer metastasis.
-These are also known as the gelatinases |
|
|
How are the MMPs regulated?
|
-The MMPS are inhibited by the tissue inhibitors of metalloproteinases
-There are |
|
|
What are the main stimuli for the angiogenic switch in tumours?
|
-Hypoxia
-inflammation -Oncogenic mutations -Mechanical stress |
|
|
Which paracrine molecules signal for angiogenesis?
|
-Angiogenin
-VEGF -Transforming growth factor-beta -Fibroblast growth factor |
|
|
Name a VEGF inihibitor?
|
-Bevacizumab
-Endogenous angiogenesis molecules may be of therapeutic value due to low-toxicity |
|
|
What is a pleomorphism?
|
-A variation in size of cells within the neoplasm
|
