Tumour-stroma interactions Flashcards
define the tumour microenvironment
defined as all the non-transformed elements residing within or in the vicinity of the tumour
Cancer cells, immune cells, CAFs, vasculature, extracellular matrix, growth factors
define the tumour microenvironment
defined as all the non-transformed elements residing within or in the vicinity of the tumour
Cancer cells, immune cells, CAFs, vasculature, extracellular matrix, growth factors
define the tumour microenvironment
defined as all the non-transformed elements residing within or in the vicinity of the tumour
Cancer cells, immune cells, CAFs, vasculature, extracellular matrix, growth factors
what does the tumour microenvironment provide the tumour?
soluble factors, ECM degrading enzymes, angiogneic factors, oxygen etc
what is the stroma?
– all the elements in the host that support the tissue
* cell types and ECM that support the function of any particular organ
* fibroblasts, adipocytes, macrophages, pericytes
* provide growth factors, cytokines, and extracellular matrix components
* Not cancerous themselves, but support tumour growth, influence therapeutic intervention, modulate gene expression
what is the tumour stroma?
Stroma becomes reactive during cancer, like a wound, wards off the danger. Host cell types infiltrate the area and try to limit damage from the rest of the body
* during cancer → stroma becomes ‘reactive’ or ‘activated’
* consists of the non-malignant cells of the tumour and extracellular matrix
* may act as a physical barrier preventing spread of tumour or therapeutic intervention
* Or may facilitate metastasis by providing growth factors, secreting ECM, or degrading ECM
what factors in the tumour microenvironment influence cell motility/metastasis?
- Hypoxia and ROS
- Cancer associated macrophages
- Cancer associated fibroblasts
- endothelial precursor cells
- ECM stiffness
- Acidity
what are the types of ECM components?
- fibrous structural proteins (collagen types, elastins)
- Protein-polysaccharide complexes to embed and regulate structural proteins (proteoglycans – decorin, biglycan, lumican) * contain glycosaminoglycan (GAG) polysaccharides
- Adhesive glycoproteins (fibronectin, laminin, tenascin) – attach to cell surface integrin receptors
what are the types of ECM rich environment present within tissues?
Basement membrane (basal lamina)
Interstitial matrix (between cells)
what are the features of the basement membrane?
- more compact and less porous
- underlying epithelial & endothelial cells, acts as barrier
- type IV collagen, laminin, fibronectin
- supports the epithelial monolayer
what are the features of the interstitial matrix?
- highly charged, hydrated, and provides tensile strength to tissues
- fibrillar collagen (type I), proteoglycans, fibronectin, tenascin-C
- connective tissue layer, contains vessel immune cells
rich in proteoglycans, brings the charge
what are the features of the interstitial matrix?
- highly charged, hydrated, and provides tensile strength to tissues
- fibrillar collagen (type I), proteoglycans, fibronectin, tenascin-C
- connective tissue layer, contains vessel immune cells
rich in proteoglycans, brings the charge
what is desmoplasia?
(desmoplastic response)
- Secondary to the formation of the cancer
- Forms around tumour and consists of cancer-associated fibroblasts
- Usually associated with malignant tumours (poor prognosis)
- Growth of hard, fibrous tissue - rich in collagen and other types of extracellular matrix as well as fibroblast cell types
what are the functions of ECM in cancer?
- barrier function can limit spread or can influence access to therapy
- can provide achorage, which can promote proliferation and cell survival
- provide functional ECM fragments (after degradation can signal)
- signal reservoir
- co receptor activating signals
- function as receptor and signal presenter
- tracks for migration
- biomechanical force
what is the transformation event that causes collagen remodelling/ ECM rigitity (in mammary gland)
loss of epithelial polarity and disruption of gland morphology
collagen realigment from wavey organisation to parallel filaments
what is the transformation event that causes collagen remodelling/ ECM rigitity (in mammary gland)
loss of epithelial polarity and disruption of gland morphology
collagen realigment from wavey organisation to parallel filaments