Pathophys 5 Flashcards
What’s tumour invasion?
The active migration of neoplastic (Tumour) cells out of their tissue of origin and into adjacent tissues of different types
What is the 3 step process of cellular invasion?
Cell attachment—>enzyme degradation of ECM—>cell migration
What is cell adhesion?
Cell connections involve between multiple Ligands and cell adhesion receptors
What is the composition of the extra cellular matrix?
Cells (fibroblasts, smooth muscle cells, chrondroblasts, osteoblasts, water)
Collegen network + what? =co gel
Non fibrillation matrix
What is the structure of the ECM?
Collegen
Elastin
Proteoglycans
Structural glycoproteins (fibronectin, laminin)
What connects Individual cells?
Cell adhesion receptors, enable cells to recognise and bind molecules on other cells or in the extra cellular matrix (ECM)
Make cells stick to other cells
Activate intracellular signalling pathways (primarily for cell death)
5 adhesion molecules
- Intigrin family
- Selectin family
- Immunoglobulin superfamily
- cadherin family
- mucin like family
What is the abbreviation for cell adhesion molecules?
CAM
Cell adhesion receptors can form:
1-homophillic adhesions-between the same type of molecules (eg, cadherins)
2-heterophillic adhesions-between different types of molecules (selectins)
What cell adhesion receptor mediates cells?
Intergrins
Others mediate cell to cell adhesion
What is an example of an intergrin?
Avb6
Where is avb6 expressed?
Only on epithelial cells and can be regulated
Does the level of avb6 increase or decrease when there is a wound?
Increase
What happens to avb6 in squamous cell carcinoma (SCC)
avb6 is upregulated on squamous cell carcinoma
When avb6 has increased expression on SCC what specifically happens?
Cell adhesion is increased
Cell migration is increased
Production of enzymes that destroy the basement membrane
SCC invasion through membrane
What do cadherins do?
Mediate Ca2+ dependant homophillic cell to cell adhesion which is used in organ formation, form desmosomes and adherens junction
Critical role in development
What happens if there is a loss of e cadherin expression?
Mutations, lead to cancer
What are the three extracellular proteinases in cancer?
1.Cathepsins–>CTS (cathepsin B, CTS S, CTS D)
2.matrix metalloproteinases (MMP’s)
Eg, gelatinases
3.serine proteinases eg, plasmin
What are MMPs roles in tumour progression?
Degradation of matrix barriers
Release of growth factors
Plays a role in morphogenisis and tissue repair
What are MMPs?
Zinc binding enzymes secreted as proenzymes
Activated in the ECM through cleavage located in the amino terminal domain
How is the MMPs function maintained?
By endogenous inhibitors of the MMPs, called tissue inhibitors of metalloproteinases (TIMPS)
What is metastasis?
The transfer of disease from 1 organ or part of an organ to another not directly connected with it
