Tumor Microenvironment and Signaling

Question 1

Answer 1

Invasive Adenocarcinoma of Colon

Question 2

Answer 2

Invasive Adenocarcinoma of Colon

Question 3

Answer 3

Invasive Adenocarcinoma of Colon

Question 4

Answer 4

Lymph node metastasis- colonic adenocarcinoma

Question 5

Answer 5

Vascular invasion, colonic adenocarcinoma

Question 6

Answer 6

Liver with metastatic carcinoma

Question 7

Answer 7

The metastatic cascade is a model of tumor dissemination

hematogenous spread

Question 8

The metastatic cascade

Answer 8

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

Question 9

Cells interact with ECM via

Answer 9

integrins

Question 10

Loosening of cell-cell adhesion mediated by

Answer 10

cadherins

Question 11

Integrins mediate interaction with

Answer 11

ECM proteins (collagens, laminin, fibronectin )

Question 12

Degredation of ECM happens by

Answer 12

proteases (MMPs (matrix metalloproteases), collagenases)

they degrade ECM proteins

Question 13

Degraded ECM may release

Answer 13

growth factors bound in ecm

ex: bFGF

Question 14

Steps to metastasis through basement membrane

Answer 14

Loosening of intercellular junctions (loosening of cell cell adhesion mediated by cadherins

Degredation of ECM (by proteases)

migration and invasion

Question 15

migration and invasion

Answer 15

autocine motility factor helps in this

Question 16

Integrins mediate

Answer 16

cell adhesion and migration

Question 17

Integrins are connected to cytoskeleton and are involved in

Answer 17

signal transduction

Question 18

Migration and invasion

Answer 18

Question 19

Degredation of ECM

Answer 19

Question 20

Loosening of intracellular junctions

Answer 20

Question 21

Answer 21

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

Question 22

Answer 22

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

Question 23

Seed and soil hypothesis

Answer 23

primary tumors preferentially metastasize to cartain sites

Question 24

Organ tropism of cancer

Answer 24

Endothelial cells at metastatic sites may express adhesion molecules or chemokines

Microenvironment may express chemokines that attract cancer cells

Question 25

Answer 25

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

Question 26

Comonents of tumor microenvironment

Answer 26

ECM (sequestered growth factors) Cancer cells Cancer associated fibroblasts pericytes endothelial cells tumor promoting inflammatory cells

Question 27

Answer 27

Components of a tumor microenvironment

Question 28

Tumor promoting anflammatory cells

Answer 28

support proteases that break down ECM

Question 29

Epithelial mesenchymal transition (EMT)

Answer 29

To acquire mitility and invasivness, cancer cells down regulate some genes and upregulate some others Process called epithelial mesenchymal transition

Question 30

Answer 30

Components of tumor microenvironment

Question 31

Answer 31

E cadherin accumulates in nucleus of tumor cells at tumor-host interface

Question 32

Epithelial mesenchymal transition (EMT) details

Answer 32

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

Question 33

Epithelial mesenchymal transition believed to favor what phenotype

Answer 33

pro-migratory

Question 34

Epithelial mesenchymal transition is the process by which

Answer 34

epithelial cells lose their polarity, cell-cell adhesion and gain migratory and invasive properties to become mesenchymal stem cells