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FMS Week 6 > Tumor Microenvironment and Signaling > Flashcards

Tumor Microenvironment and Signaling Flashcards

1
Q
A

Invasive Adenocarcinoma of Colon

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2
Q
A

Invasive Adenocarcinoma of Colon

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3
Q
A

Invasive Adenocarcinoma of Colon

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4
Q
A

Lymph node metastasis- colonic adenocarcinoma

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5
Q
A

Vascular invasion, colonic adenocarcinoma

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6
Q
A

Liver with metastatic carcinoma

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7
Q
A

The metastatic cascade is a model of tumor dissemination

hematogenous spread

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8
Q

The metastatic cascade

A

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

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9
Q

Cells interact with ECM via

A

integrins

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10
Q

Loosening of cell-cell adhesion mediated by

A

cadherins

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11
Q

Integrins mediate interaction with

A

ECM proteins (collagens, laminin, fibronectin )

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12
Q

Degredation of ECM happens by

A

proteases (MMPs (matrix metalloproteases), collagenases)

they degrade ECM proteins

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13
Q

Degraded ECM may release

A

growth factors bound in ecm

ex: bFGF

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14
Q

Steps to metastasis through basement membrane

A

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

Degredation of ECM (by proteases)

migration and invasion

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15
Q

migration and invasion

A

autocine motility factor helps in this

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16
Q

Integrins mediate

A

cell adhesion and migration

17
Q

Integrins are connected to cytoskeleton and are involved in

A

signal transduction

18
Q

Migration and invasion

A
19
Q

Degredation of ECM

A
20
Q

Loosening of intracellular junctions

A
21
Q
A

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

22
Q
A

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

23
Q

Seed and soil hypothesis

A

primary tumors preferentially metastasize to cartain sites

24
Q

Organ tropism of cancer

A

Endothelial cells at metastatic sites may express adhesion molecules or chemokines

Microenvironment may express chemokines that attract cancer cells

25
Q
A

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

26
Q

Comonents of tumor microenvironment

A

ECM (sequestered growth factors)

Cancer cells

Cancer associated fibroblasts

pericytes

endothelial cells

tumor promoting inflammatory cells

27
Q
A

Components of a tumor microenvironment

28
Q

Tumor promoting anflammatory cells

A

support proteases that break down ECM

29
Q

Epithelial mesenchymal transition (EMT)

A

To acquire mitility and invasivness, cancer cells down regulate some genes and upregulate some others

Process called epithelial mesenchymal transition

30
Q
A

Components of tumor microenvironment

31
Q
A

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

32
Q

Epithelial mesenchymal transition (EMT) details

A

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

33
Q

Epithelial mesenchymal transition believed to favor what phenotype

A

pro-migratory

34
Q

Epithelial mesenchymal transition is the process by which

A

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

FMS Week 6 (12 decks)

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