Tumor Microenvironment and Signaling Flashcards
Invasive Adenocarcinoma of Colon
Invasive Adenocarcinoma of Colon
Invasive Adenocarcinoma of Colon
Lymph node metastasis- colonic adenocarcinoma
Vascular invasion, colonic adenocarcinoma
Liver with metastatic carcinoma
The metastatic cascade is a model of tumor dissemination
hematogenous spread
The metastatic cascade
Transformed cell- clonal expansion, growth, diversification, and angiogenesis. Starts primary tumor.
Metastatic subclone adheres to basement membrane and invades it.
Passage of metastatic cell though ECM
Intravasion into blood vessel
Interaction with host cell lymphocyte (lymphoid cells)
Tumor cell embolus (multiple tumor cells with patelets)
Adhesion to basement membrane of vessel
Extravasion into EMCC of another tissue
metastatic deposit
angiogenesis
growth
Cells interact with ECM via
integrins
Loosening of cell-cell adhesion mediated by
cadherins
Integrins mediate interaction with
ECM proteins (collagens, laminin, fibronectin )
Degredation of ECM happens by
proteases (MMPs (matrix metalloproteases), collagenases)
they degrade ECM proteins
Degraded ECM may release
growth factors bound in ecm
ex: bFGF
Steps to metastasis through basement membrane
Loosening of intercellular junctions (loosening of cell cell adhesion mediated by cadherins
Degredation of ECM (by proteases)
migration and invasion
migration and invasion
autocine motility factor helps in this
Integrins mediate
cell adhesion and migration
Integrins are connected to cytoskeleton and are involved in
signal transduction
Migration and invasion
Degredation of ECM
Loosening of intracellular junctions
View of ECM. Looking at integrins and how they interact with the ECM. Integrins are attached to focal adhesion molecules inside the cell which are tethered down to the actin cytoskeleton. On the outside of the cell, integrins are connected to laminin fibers which interact with fibronectin and collagen. Integrins are heterodiners composed of alpha and beta chains
Image showing that heparan sulfate proteoglycan in matrix. Heparan interacts with GFs and they make complex with GFs (bFGF)
Syndecan interacts with haparan and actin cytoskeleton
When a tumor breaks down ECM, it can release growth factors
Seed and soil hypothesis
primary tumors preferentially metastasize to cartain sites
Organ tropism of cancer
Endothelial cells at metastatic sites may express adhesion molecules or chemokines
Microenvironment may express chemokines that attract cancer cells
View of cancer
You can see that there are cancer cells, cancer stem cells, immune inflammatory cells, invasive cancer cells, endothelial cells, cancer associated fibroblasts ect
Comonents of tumor microenvironment
ECM (sequestered growth factors)
Cancer cells
Cancer associated fibroblasts
pericytes
endothelial cells
tumor promoting inflammatory cells
Components of a tumor microenvironment
Tumor promoting anflammatory cells
support proteases that break down ECM
Epithelial mesenchymal transition (EMT)
To acquire mitility and invasivness, cancer cells down regulate some genes and upregulate some others
Process called epithelial mesenchymal transition
Components of tumor microenvironment
E cadherin accumulates in nucleus of tumor cells at tumor-host interface
Epithelial mesenchymal transition (EMT) details
in EMT carcinoma cells downregulare cetain genes and upregulate others
they downregualre epithelial markers (eg e cadherin)
Upregulate mesenchymal markers (vimentin and smooth muscle actin)
Transcription facots that regulate EMT include SNAIL, TWIST, and ZEB
Epithelial mesenchymal transition believed to favor what phenotype
pro-migratory
Epithelial mesenchymal transition is the process by which
epithelial cells lose their polarity, cell-cell adhesion and gain migratory and invasive properties to become mesenchymal stem cells
