ECM Flashcards
List the components of the ECM and their functions
PG covalently attached to GAG- hydrated gel that allows diffusuon of metabolites, hormones, nutrients. Attaches to proteins to provide a compressive force
Collagen- abundant provides strength and organization, can be fibrillar or non fibrillar
Specialized proteins such as elastin(Resilience), laminin(adhesion), fibronectin(adhesion)
Growth factors
Lectin
complementary factors
tissue transglutamidase
How is the ECM synthesized and degraded
Most molecules are synthesized by fibroblasts or specialized fibroblasts. They are made intracellularly and secreted into the ECM and organized by the cells.
They are degraded by metalloproeinases that degrade the basement membrane and all of the components
How is ECM involved in cancer, give specific examples
MMPs can be deregulated and release growth factors can bind to heparan sulphate found in perlecans or laminin and induce angiogenesis, it will activate the VEFGR/AKT pathway.
How can ECM support cell growth and metastasis in cancer
The ECM is remodelled and influences the cell behaviour because they are connected through integrin and vice versa changes in the cells will change it’s organization outside in- signalling and inside out signalling.
When ECM are disorganized the cells will be de-differentiated because PG give their identity and ECM organization.
Degradation of the basement membrane will occur, proteolysis will release growth factors and pro-angiogenic factors, angiogenic switch will go toward angiogenesis that will bind to heparan sulphate and induce cell growth angiogenesis and metastasis.
Like a wound that doesn’t heal, it will recruit macrophages, pro inflammatory molecules which will feed the cycle
How do they model the matrix and cancer?
By using the matrigel, which is ECM from a tumour, it is rich witch components and at room temperature can model the biological system of ECM. Patient derived xenograft models In-vitro organoid system Bespoke hydrogel 3D culture
