EMT + metastasis Flashcards

1
Q

Define metastasis

A

spread of malignant cells from the primary tumour to other, independent sites within the body

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2
Q

Explain how metastasis is a multistep process

A

Carcinogenesis -> angiogenesis -> Detachment/invasion -> Intravasation -> migration -> extravasation -> micrometastasis -> macrometastasis

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3
Q

Features of angiogenesis:

A

Formation of blood supply (vascularisation) of tumour

occurs following transformation and initial growth of cells

At tumour size >1 mm, diffusion of nutrients and waste products become rate limiting for continued growth of tumour
-Angiogenesis must occur to provide support for growth of the tumour mass

Synthesis and secretion of pro-angiogenic factors (fibroblast growth factor, FGF; vascular endothelial growth factor, VEGF) by tumour cells and other non-cancerous cell types around cancer

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4
Q

How do cells become metastatic?

A

Initial growth of cancerous cells and formation of a tumour, developing a vascular supply

factors produced by cancerous cells and surrounding non-cancerous cell types stimulate morphological changes in cells

Phenotypic conversion and dedifferentiation of epithelial cells – indicative of carcinoma (epithelial derived cancer)

Characterised by epithelial mesenchymal transition (EMT) enabling cells to migrate and invade the surrounding tissue; invasion of the vascular and lymphatic system → resulting in metastasis

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5
Q

Who proposed the ‘seed and soil’ hypothesis and what is it?

A

Proposed by Stephen Paget (1889) – distribution of metastases is not by chance, instead metastases develop only when ‘seed’ and ‘soil’ are compatible

‘seeds’ - cancer cells with metastatic ability

‘soil’ - microenvironment

3 principle factors

Tumours are heterogeneous made up of cancer cells with subpopulations of host cells (e.g. epithelial, fibroblast, endothelial, leukocytes) exhibiting different properties (angiogenic, invasive, metastatic, growth rate)

Metastasis is selective for cancer cells which demonstrate a combination of these particular properties

Success of the resulting metastasis at the secondary site depends on its ability to interact with and utilise the ‘soil’, comprising multiple factors within the microenvironment

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6
Q

Does bi-directional movement between primary and distant tumour sites exist?

A

Yes

metastases have the ability to re-seed the primary tumour site

suggests that local environments within each site are similar and conducive to tumour growth

This may occur during relapse of disease, following initial treatment phase

Larger the arrow, more common spread to this place happens

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7
Q

Epithelial cells location/function

A

Epithelium sits on top of the connective tissue layer (stroma) – basal lamina (basement membrane – rich in ECM) separates the 2 compartments

Have a barrier function to protect the underlying tissue and also act to selectively sort molecules (by secretion, absorption) between the lumen and the underlying tissue

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8
Q

what is epithelia derived cancer?

A

Development of cancerous growth within the epithelium, leads to disruption of tissue organisation and eventual invasion into the connective tissue layer

colon, breast, ovary, lung, prostate, pancreas – common sites of epithelial-derived cancers

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9
Q

Epithelial cell structure

A

Polarised cells – has apical and basal domain, and differentiated

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10
Q

Explain the epithelial junctional complexes

A

Electron microscopy shows 3 sections (Fawcett 1966)

Tight junctions – zipper-like, restricts flow of molecules e.g. ZO-1 and water within the intercellular space, maintains impermeable epithelial barrier

Adherens junctions – (E-cadherin) – provides lateral adhesion between neighbouring epithelial cells – maintains actin contractile ring and epithelial polarity

Desmosomes – linked to intermediate filaments (e.g. cytokeratin), functions to maintain adhesion and tissue integrity

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11
Q

Describe E-cahedrin cell-cell junctions

A

Ca2+ dependent homodimerization of E-cadherin

linked to actin cytoskeleton

Provides structural support for tissue organisation

supports apical/basal polarity of individual epithelial cells by maintaining actin contractile ring - adhesion belt

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12
Q

Describe cell-cell adherens junctions

A

Actin contractile ring linked to cell-cell junctions maintains the adhesion belt between cells

Provides structural support to tissue and maintains columnar epithelial phenotype

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13
Q

What is EMTand ref first discovered

A

Epithelial-mesenchymal transition

First described by the lab of Elizabeth Hay, 1982 – occurs during development of embryo

Reversible phenotypic conversion of polarised (differentiated) epithelial cells to unpolarised mesenchymal cells

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14
Q

If you were to look under a microscope at cancer cells undergoing EMT, how would you distinguish between epithelial cells and mesenchymal cells?

A

Epithelial:
E-cahedrin and b-catenin and cell-cell junctions

Mesenchymal:
Loss of E-cahedrin
B-catenin is cytoplasmic

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15
Q

How does the TME influence EMT?

A

Tumour microenvironment provides factors and different cell types that promote cancer cell dedifferentiation and metastasis

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16
Q

What factors promote metasiasis and EMT

A

TNFa and IL-1b : pro-inflammatory cytokines that promote remodelling, EMT, invasivness

Secretion of growth factors and ECM - promote cell proliferation, EMT, cell migration/invasion

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17
Q

Features of Transforming growth factor beta1 (TGFβ1)

A

Secreted growth factor, usually has a tumour supressor function

Some oncogenes e.g. Myc, when mutated, allows cells to bypass the checkpoint control of TGFb1

This causes accumulation of TGFb1 and causes it to have a tumour promoting function, promotes EMT invasion/motiliy and inirectly effects angiogenesis and immunosupression

Haynes 2011

learn diagram

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18
Q

Differences in actin between epithelial and mesenchymal

A

Epithelial:
Cortical actin ring

M:
Actin stress fibres

(can see this in the microscope when you add TGFb1 to E cells - see these fibres - Margaret 2008)

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19
Q

Explain what latent TGFb1 is

A

TGFβ1 kept in latent (inactive) form in complex with latent associated peptide (LAP) derived from N-terminal region of TGFβ1 precursor

active/mature TGFβ1 derived from C-terminus, activated by factors - MMPs, ROS, acidic pH, ECM

Heterodimerisation of type I and II receptors, leads to a kinase cascade

Recruitment of R-SMAD (Smad2/3) and phosphorylation

Translocation into nucleus and modulation of gene expression

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20
Q

Factors of epithelial cells

A

E-cadherin

cytokeratin

ZO-1

Desmoplakin

Laminin

Low cell motility, cell-cell adhesion

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21
Q

Factors of mesenchymal cells

A

N-cadherin

Vimentin (intermediate filament)

fibronectin

α5β1 integrin receptor

Twist

Slug

Snail

Alpha-smooth muscle actin

High cell motility, cell-ECM adhesion, ECM production and deposition

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22
Q

How is EMT regulated?

A

EMT is a result of transcriptional reprogramming:

Wnt
Transforming growth factor β1 (TGFβ1)
Notch
Epidermal Growth Factor (EGF)
Hepatocyte Growth Factor (HGF)
Tumour necrosis factor α (TNFα)

cause changes in TFs - ZEB1/2, Snail, Twist

leads to either EMT (high vimentin, low E-cad) or MET (Low vimentin, high E-cad)

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23
Q

Role of ZEB

A

ZEB1 – activates DNA repair pathways, promotes cell survival → in an EMT-independent and dependent manner

p53 inhibits ZEB1 expression via microRNA 200 – upon p53 deletion, ZEB1 becomes active and is able to induce EMT; p53 represses Snail expression

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24
Q

Regulation on EMT by miRNAs

A

microRNA 200 negatively regulates expression of ZEB1, thus inhibiting EMT

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25
Q

Post-translational regulation of EMT

A

Snail can be phosphorylated at 1st site by GSK3β which leads to its translocation out of the nucleus (e.g. in absence of Wnt signalling)

In the cytoplasm, Snail subsequently gets phosphorylated by GSK3β at 2nd site, leading to its ubiquitination and targeting to the proteasome for degradation

Alternatively, wild-type p53 induces the mdm2-dependent ubiquitination and degradation of Snail

Downregulation of Snail leads to an inhibition of cell migration and invasion

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26
Q

Whats a key feature of promoting mesenchymal cell migration?

A

Remodelling of the actin cytoskeleton:

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27
Q

Functions of the actin cytoskeleton

A

driving membrane protrusion

Cell shape changes

Maintaining cell-ECM linkages

Cell contraction

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28
Q

When the TGFb1 receptor gets activated, apart from production of EMT regulator genes, what else happens?

A

Actiation causes activation of RhoGTPases, which causes the disassembly of adherin junctions and remodelling of the actin cytoskeleton

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29
Q

briefly describe the Rho GTPase cycle:

A

Rho with bound GDP = inactive
GEF changes GDP for GTP, Rho with bound GTP is actuve and activates effectors and downstream pathways

GAP switches GTP for GDP (making it inactuve)

GDI (guanine nucleotide dissociation inhibatir) keeps Rho+GDP bound by binding itself to it (reversable)

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30
Q

Give examples of constituativly active GTPases and how expression causes changes in the actin cytoskeleton

A

All seen microscopically (Hall 1998)

RhoA activation: Actin stress fibres and focal adhesion

Rac1 activation: Lamellipodia formation - > actin rich membrane ruffles/small focal adhesion contacts

Cdc42 activation: Filopodia formation -> finger-like actin protrusions

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31
Q

Rho family effectors and function:

A

Rho family members - bound GTP to be active

Effector proteins interact with GTP-bound Rho protein

Kinases and actin binding proteins modulate actin

e.g.s of Rho family:
Rho - contractile phenotyping
Rac - Actin polymerisation, actin branching
Cdc42 - Actin polymerisation, filopodia

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32
Q

Features of focal adhesions

A

multiprotein complex at the plasma membrane interface – this interaction with extracellular matrix (ECM) mediated by integrin receptors on cell surface

actin-binding proteins [α-actinin, vinculin, myosin], signalling proteins [p130Cas, Src, focal adhesion kinase (FAK)], structural proteins [paxillin, talin], integrin receptor

provides tensile strength, cell shape, and facilitates membrane protrusion and cell migration – promotes cancer metastasis

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33
Q

Integrin receptor family:

A

Heterodimeric receptors comprising an alpha chain and beta chain – link internal actin cytoskeleton to ECM (except α6β4)

Different combinations interact with specific extracellular matrix proteins → provide links from inside to outside of cell

(combination of alha and beta components provides specificity

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34
Q

Explain focal adhesion signalling

A

Diamerised integrins, interacting extracellularly with the ECM, have attached intracellularly a series of molecules:

vinculin and talin – actin binding proteins

paxillin – adaptor protein

FAK - structural support and signalling platform

Src – tyrosine kinase, signals to Ras (MAPK cascade) and causes Rho GTPase activation

This leads to actin cytoskeleton remodelling and focal adhesion formation

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35
Q

What faciliates cell movement?

A

Focal adhesions and actin cytoskeleton

36
Q

Steps to cell movement:

A
  1. extension - actin polymerisation and branching facilitates this
  2. Adhesion - focal adhesion formation
  3. Translocation - retraction facilitatied by increased tension/contraction
  4. De-adhesion - focal adhesions break down
37
Q

Describe the leading edge of a migrating cancer cell

A

Actin-rich membrane ruffles

lamellipodium

38
Q

How does the actin cytoskeleton work?

A

A linear actin filament (F-actin) is made up of many individual globular actin (G-actin) monomers

Each molecule of actin is bound to either ATP or ADP

ATP-G-actin is added to the growing (plus) end of the filament and ADP-G-actin is disassembled from the retreating (minus) end of the actin filament

39
Q

Explain actin cytoskeleton organisation at the leading edge of a migrating cell

A

Lamellipodium further bacj, Filopodium right at the edge

Lamellipodium are branched actin, Filopodium are parallel actin, both still have the plus and minus end

40
Q

Explain actin cytoskeleton regulators and cell migration

A

At the uropod (cell end where migration has come from) - RhoA activation -> ROCK -> pMLC -> increased myosin contractility (actin here is rich in myosin-II -> cross-links actin and contributes to contractility)

At the leading end of the cell:
Rac1 -> WAVE
Cdc42 -> WASP

both lead to Arp2/3 activation that promotes branched actin (therefore lamellipodium formation)

Cdc42 also leads to mDia (Formin) activation, which is an actin nucleator that promotes actin polymerisation (Filopodia formation)

41
Q

How can collective cell migration be identified

A

Intact cell-cell junctions

42
Q

Types of cell migration

A

Collective migration: cell-cell and cell ECM interactions (with some leading cells to cause movment)

Mesenchymal cell migration: utelises interactions with the ECM to migrate

Amoeboid migration: doesn’t depend on ECM, finds path though chemoattractants

Scaffold cell-dependant migration (cell-cell dependant interactions)

43
Q

difference in breast epithelial cells compared to mesenchymal

A

E - form islands, group together

M - Dont group as much, dont form islands

44
Q

Mesenchymal vs. collective cell migration

A

Mesenchymal & collective – both path-generating

Collective – retains cadherin cell-cell junctions, while only exhibiting focalised cell-matrix adhesions and ECM degradation in leader cells

RW

45
Q

Table of amoeboid (collective) vs mesencymal

A

M Vs. A
Migration stratagy: Path generating Path finding

Mechanisms for. Proteolytic ECM. Mprphalogical
overcomig tissue barriers: Degradation. Adaptation

Composition of
cell-ECM interactions: Focalised Diffuse(integrin-R)
integrin-Rs clustered non-clustered

46
Q

MMP features

A

Zn2+ dependent proteases secreted by cells into extracellular space

secreted as an inactive pro-form and following activation in the extracellular space they cleave extracellular matrix proteins and/or activate latent TGFβ1

Regulate migration, invasion, proliferation, differentiation, angiogenesis

47
Q

The action of MT1-MMP in cancer cells

A

MT1-MMP directly degrades ECM (e.g. basal lamina), allowing cells to invade into underlying connective tissue layer

MT1-MMP can activate MMP-2 within connective tissue layer, thus further facilitating cancer cells ability to migrate and invade surrounding tissue

MT1-MMP (membrane bound) – transmembrane metalloprotease → directly remodels extracellular matrix (fibronectin, collagen, laminin, vitronectin)

48
Q

Whats a natural inhibator MMP

A

TIMP-2

49
Q

In terms of MMPs, what is indirect remodelling through?

A

activation of MMP2

50
Q

Steps of remodelling and MMP-2 activation

A
  1. MT1-MMP monomer expression on the cell surface
  2. MT1-MMP dimerization through Hpx and TM domain
  3. Formation of activation complex of dimer MT1-MMP, TIMP-2 and proMMP-2
  4. Propeptide cleavage by MT1-MMP free from TIMP-2
  5. MMP-2 activation by free MT1-MMP subunit by cleavage followed by release of active MMP-2
51
Q

What does TIMP-2 stand for?

A

Tissue inhibitor of metalloproteinase 2

52
Q

What do levels of TIMP-2 regulate

A

MMP activation

53
Q

Sites of ECM degradation - invadopodia formation

A

Cell protrusions of the plasma membrane – filopodia-like structures - actin rich

secrete MMPs and degrade extracellular matrix

54
Q

Mechanisms of metastasis

A

Initiation - by Src kinase

Assembly - by proteins attainh to actin

Maturation - microtubules connect to the actin

RW to check this is correct

55
Q

Define the TME

A

defined as all the non-transformed elements residing within or in the vicinity of the tumour:

Cancer cells

Immune cells

Cancer-associated fibroblasts

Vasculature

Extracellular matrix

56
Q

Normal stroma features

A

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

57
Q

Features of tumour stroma

A

normal stroma - essential for maintenance of epithelial tissue and regulates tissue homeostasis

communication between stroma and epithelial cells by direct cell-cell contact or secreted factors

during cancer → stroma becomes ‘reactive’ or ‘activated’ - like a wound response to danger signal

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

58
Q

Factors in the tumour microenvironment influencing cell motility/metastasis

A

ROS - caused by hypoxia, CAMS and CAFs

RNS - caused by CAMs

Endothelial precurosir cells

ECM stifness

Acidity (lowering of pH)

59
Q

Define ECM

A

molecules secreted by cells that provide structural support and biochemical interactions

composed of proteins, glycoproteins, proteoglycans, and polysaccharides – give structura; support ans organisation

Some proteins interact with cell surface receptors

60
Q

Types of ECM components:

A

molecules secreted by cells that provide structural support and biochemical interactions

composed of proteins, glycoproteins, proteoglycans, and polysaccharides – give structura; support and organisation

Some proteins interact with cell surface receptors

61
Q

What happens to the ECM in cancer

A

Upregulation of various collagen types, fibroectin, proteoglycans

62
Q

Types of ECM rich environments within tissues

A

Basement membrane (basal lamina) - provides separation between different tissues:

  • more compact and less porous
  • underlying epithelial & endothelial cells, acts as barrier
  • type IV collagen, laminin, fibronectin

Interstitial matrix (between cells):

  • highly negatively charged, hydrated, and provides tensile strength to tissues (able to handle large amounts of stress before it breaks)
  • fibrillar collagen (type I), proteoglycans, fibronectin, tenascin-C
63
Q

Explain desmoplasia

A

also called desmoplastic response:

Secondary to the formation of the cancer

Forms around tumour and consists of cancer-associated fibroblasts (myofibroblasts – have muscle cell characteristics, e.g. alpha-smooth muscle actin), they can remodel the ECM

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

64
Q

Name of the stain used to show increased collegen in desmoplasia

A

Masson’s trichome stain (blue for collagen)

65
Q

Mechanisms of ECM function in cancer

A

Barrier to therapy

Signallig to cancer cells

Biomechanical force

ECM fragments can also signal, and act as a co-receptor activating signal

Act as cell migration tracks for cancer cells to metastisize

66
Q
A
67
Q

Mammary gland transformation and influence of ECM stiffening:

A

Epithelial cells become disrupted and apical basal polarity is lost, normal gland morphology is lost and ECM is remodelled as tumour progression continued, creates lined fibrils

68
Q

Influence of ECM Rigidity (tension)

A

Increased ECM deposited = increased ECM tension/regidity - this negatively correlates with patients survival

69
Q

Stromal cell remodelling of the ECM:

A

TACS= tumour associated collegen signatures

Normal ECM (TACS-1):
Basement membrane, normal fibroblasts, epithelial cells

Predisposed (TACS-2):
Pre-alligned collagen, Protease and other factors, cancer cells, CAFs

Desmoplasmic ECM (TACS-3):
stiffness from collagen, reduced elasticity, intravasation of cancer cells

70
Q

What does TACS stand for?

A

Tumour-associated collagen signature

71
Q

Hypoxia and tumour metastasis

A

Hypoxia Inducible Factor 1α (Hif1α) transcription factor – regulated by intracellular oxygen levels → as levels of oxygen decrease, Hif1α protein is not degraded (due to not being hydroxylated) by proteasome and accumulates in the cell

This leads to overexpression of plasma membrane receptors (e.g. Met receptor) or angiogenic factors (VEGF), also leads to increased sensitivity to growth factors such as HGF (ligand for MetR)

leads to:
ECM degradation, EMT, chemotaxis - seek O2 rich regions, angiogenesis

72
Q

How much stiffer is breast cancer tissue than normal tissue

A

10x

73
Q

Features of LOX

A

copper dependent amine-oxidase

upregulated in a variety of tumours in response to hypoxia (regulated by Hif1α)

Oxidizes peptidyl-lysine residues, resulting in reactive aldehydes, leading to inter and intra molecular covalent crosslinks

cross-links collagen fibers and other ECM molecules (elastin)

promotes ECM stiffening and tumour invasion

74
Q

What leads to ECM stiffening

A

increased integrin signalling and focal adhesion formation, enhanced PI3 kinase activity, increased cell invasion

75
Q

The Warburg effect

A

First described by Otto Heinrich Warburg in 1924

It was observed that cancer cells produce energy by a high rate of glycolysis (they rely on higher levels of glycolysis)

Production of lactic acid by tumour cells due to anaerobic glycolysis rather than oxidative phosphorylation for energy production – cancer cells rely on glycolysis even if oxygen is available

High lactate leads to a high proton concentration → therefore an acidic environment

76
Q

Cancer Imaging – based on cancer cell metabolic activity:

A

Positron emission tomography (PET) with 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG) (a glucose analogue that doesn’t get broken down) – measures gamma radiation from radioactive isotope

Exploits cancer cells increased glucose uptake and glycolytic activity

observes metabolic abnormalities before phenotypic changes

Sensitive technique

Can be used to monitor patient’s response to chemotherapy based on metabolic activity (responders and non-responders) - before any reduction in tumour size occurs

77
Q

Example of PET scan after cancer treatment

A

Patient with Hodgkin’s lymphoma - treated with Sirolimus (mTOR inhibator) and vorinostat (Histone deacetylase inhibator) for three cycles, PET scans taken befor and after

showed large decrease in glycolytic activity indivcationg cancer cell decrease

Subbiah et al 2014

78
Q

Hypoxia and an acidic microenvironment

A

External pH of solid tumours is acidic due to increased metabolism of glucose as well as poor fluid and gas exchange (perfusion)

Activates stress pathways (Reactive oxygen species), inflammatory response – inducing chromosomal instability

stimulates the secretion of lysosomal proteases (cysteine cathepsins) and active collagenases (matrix metalloproteinases)

79
Q
A
80
Q

Fibrobalsts in cancer

A

Mesenchymal stromal cells, exhibit cell plasticity – different phenotypes depending on tissue of origin/function

Normal fibroblasts – reside within connective tissue (interstitial matrix) and synthesise and remodel the extracellular matrix; quiescent (non-dividing) under normal circumstances, just provide a supporting role

Cancer associated fibroblasts

Originate from activation of normal fibroblasts by tumour derived growth factors or may result from endothelial to mesenchymal transition (EndMT)

TGFβ1, PDGF, bFGF

Triggers conversion of fibroblasts, immune cells, pericytes, smooth muscle cells, adipocytes (many normal cell types can turn into CAFs)

Increased proliferation rate, enhanced ECM production and ECM remodeling – enhance tumourigenesis

81
Q

CAF features

A

CAFs facilitate transformation – may infiltrate the tumour or reside at the tumour margins

CAFs:

Express high levels of alpha-smooth muscle actin, fibroblast specific protein 1, extracellular matrix (e.g. periostin, tenascin-C), fibroblast activation protein (FAP)

FAP – type II integral membrane serine protease; restricted to reactive fibroblasts; detected on the surface of fibroblasts in stroma surrounding >90% of epithelial cancers; may have role in matrix digestion, immunosuppression e.g. of NK cells

secrete growth factors – promote paracrine signaling

Example: Stroma derived factor 1 (SDF-1α)/CXCL12 interacts with CXCR4 (receptor) on tumour cells and promotes cell migration

82
Q

SDF-1/CXCR4 signaling:

A

Fibroblasts react to local environment e.g. higher levels of TGFb1, causing change of a cell into a CAF, this then drives growth factors e.g. SDF-1, this causes autocrine signalling loop driving differentiation/activation of fibroblasts, and a paracrine signaling pathway (SDF-1 binds to CXCR4 receptor) causing increase cell proliferation and motility of cancer cell itself (by increasing signaling pathways e.g. ERK1/2, PI3K/Akt) SEE DIAGRAM

83
Q

Other functions of CAFs

A

Tumour angiogenesis:

releasing growth factors (VEGF, FGF)

recruiting endothelial precursor cells

Extracellular Matrix (ECM):

-Remodeling ECM architecture, exposing cryptic binding sites (allowing for alternative interactions to occur)
–promotes cancer cell migration

-ECM stiffening
–modulate intercellular adhesion and cell contractility – disrupts tissue organisation, promotes cell migration

Tumour-related inflammation:

-Recruiting immune cells (monocytes, macrophages)

-Modulate function of immune cells
–Pro-inflammatory signalling
–Inhibiting Natural Killer cell and CD8+ cytotoxic T-lymphocyte function

84
Q

Tumour stroma and its influence on cancer therapy

A

Ligands derived from activated fibroblasts may signal to receptor (e.g. receptor tyrosine kinases) on tumour cells (paracrine signalling) – leading to therapeutic resistance (e.g. pro-survival signalling)

Fibroblasts and extracellular matrix may provide a physical barrier or an avenue for metastasis

Impaired drug delivery –

  • Density of the tumour stroma
  • Lack of vasculature
  • inefficient blood flow
85
Q

Name an autofluorescent chemotherapeutic drug for treatment of pancreatic ductal carcinoma

A

Doxorubicin

RW

86
Q

Immune system in the TME

A

Infiltration of immune cells, such as macrophages, contributes to cancer progression – promoting survival and immunosuppressive environment

Release of pro-inflammatory cytokines, such as TNFα, may also promote survival and resistance to chemotherapy

87
Q
A