Cancer biology part 2

Question 1

what is P53?

Answer 1

its a tumour suppressor gene that responses to damage and helps with DNA repair can put a holt on the cell cycle

Question 2

if a gene is damaged too much what will P53 do?

Answer 2

it will instigate apoptosis rather than letting the cell divide still

Question 3

how does P53 induce apoptosis?

Answer 3

• P53 inhibits Bcl-2 a pro-survival protein
• activates Baxa cell death effector which causes mitochondrial outer membrane permeabilisation and release of cytochromee c into the cytosol
• then triggering caspase-3 activation

Question 4

what happens if P53 is abnormal?

Answer 4

-these cells can undergo apoptosis and mutated cells aren’t eliminated or repaired so will have tumorigenesis

Question 5

what causes genomic instability?

Answer 5

• loss or mutation of P53
• breakdown of one or more DNA repair mechanism e.g. DNA mismatch repair, base excision repair
• mutagenic agents and viruses
• a combination of these factors

Question 6

what are telomeres?

Answer 6

they are protective caps at the end of repetitive dna at the end of chromosomes and consisit of hexameric TTAGGG nucleotides. prevent unraveling, each time the cell divides the telomeres get shorter

Question 7

what is the crisis point?

Answer 7

when they cell realises that there are damaged bits of DNA cell will go into a long term sleep known as senescence or apopotsis

Question 8

what is telomerase?

Answer 8

a cellular reverse transcriptase that adds DNA sequences onto telomeres to prevent shortening

Question 9

how do tumour cells bypass the crisis point?

Answer 9

by up-regulating telomerase and avoiding cell cycle checkpoint genes like p53 p21 p16 and Rb

Question 10

what is the most common point mutation in cancer?

Answer 10

telomerase promoter mutations

Question 11

what are cancer stem cells?

Answer 11

they sit in the tumour and are resistant to chemotherapy

Question 12

why chemotherapy doesn’t always work?

Answer 12

• due to metastatic CSC
• some cells are chemorefractory CSC
• stem cells cells arent actually targeted

Question 13

how may cancer come back if CSC aren’t fully treated?

Answer 13

because there can be a second mutation in the single CSC that remained to form other CSC

Question 14

what allows for targeting cancer stem cells?

Answer 14

• their expression of specific markers (CD133, CD 44, CD24)

- they also have high amount of enzymes like (aldehyde dehydrogenase-ALDH)

Question 15

what else should we consider in the tumour microenvironment?

Answer 15

oxygen concentration

Question 16

what are the two types of microenvironments to do with oxygen that a tumour can have?

Answer 16

hypoxia and normoxia

Question 17

what happens when the tumour cells experience hypoxia?

Answer 17

cells could go into dormant

Question 18

what do hypoxic cancer cells have which is bad for the growing tumour?

Answer 18

-tumour cells further away from the blood capillary have an increased genetic instability meaning mutations can occur
-poor immune response
-HIF1-alpha expression
results in altered
angiogenesis
• Less susceptibility to
chemotherapy and
radiation therapy

Question 19

what is HIF-1-alpha?

Answer 19

gene that responses to different levels of oxygen conc

Question 20

what does Lack of oxygen delivery to cells and

impaired waste removal causes?

Answer 20

necrosis

Question 21

what happens when a cell dies by necrosis?

Answer 21

it the spilling of cellular
contents causing inflammation and
injury to nearby cells
-Evokes an inflammatory response

Question 22

how can p53 affect hypoxic tumour cells?

Answer 22

if p53 has a mutation then cells can just grow with hypoxia so have selective survival

Question 23

what helps the tumour grow and develop?

Answer 23

-new blood vessels will start to form and provide the tumour with oxygen and nutrients and evacuate metabolic waste and CO2

Question 24

what is neoangiogenesis?

Answer 24

promoting the formation of new blood vessels

Question 25

how do you know that the angiogenic switch has occurred?

Answer 25

Tumour secretion
of angiogenic
factors like GF and MMP simulates
angiogenesis causing proliferation of tumour

Question 26

what does MMP do?

Answer 26

it degrades extracellular matrix which can lead to tumour spreading into blood vessles

Question 27

what is the organisation of blood vessels like in a tumour cell?

Answer 27

-disorganised, irregular not all cells will get enough oxygen and nutrients

Question 28

overall what does angiogenesis do?

Answer 28

supports tumour growth and metastasis

Question 29

what is intravasation?

Answer 29

when a tumour cell breaks away from the rest and enters he blood vessel

Question 30

how do tumour cells get separated?

Answer 30

MMP cleaves cell surface protein E-cadherin and tumour cell released
from tumour.
-MMP can also process or activate
cytokines or growth factors in the
tumour microenvironment
-MMP cleaves ECM and
tumour cell released.

Question 31

what causes tumour migration with the help of macrophages?

Answer 31

Growth factors and
chemokines are secreted by
macrophages (in addition to
MMPs) to cause tumour cell
migration

Question 32

how do tumours affect macrophages to prevent the prevention of tumour migration?

Answer 32

In a reciprocal fashion, tumour
cells secrete factors that
affect macrophage function /
chemotaxis

Question 33

what are pericytes?

Answer 33

. Pericytes (gatekeepers of the
blood vessels) secrete factors
(e.g. CXCL12) that cause
tumour cell

Question 34

how do tumour cells in the blood vessel evade NK cells?

Answer 34

they aggregate platelets and arent recognised by NK cells to prevent death

Question 35

how do cancer cells obtain their energy?

Answer 35

-Cancer cells alter their metabolism to obtain energy from alternate sources that a
normal cell typically does not use and so diverts metabolites for useful anabolic
processes such as mitosis.
-Cancer cells are very different, where they can convert glucose to lactate
irrespective of the presence of oxygen.

Question 36

how can cancer cells be killed by NK cells?

Answer 36

• Recognise stressed cells
• Detect downregulation of MHC-I in the tumour cells
• Can signal directly to T cells
• Can present antigen to dendritic cells to start the process of cytotoxic T cell
(CTL) activation
• CD8 Cytotoxic T lymph

Question 37

how to distinguish self and non self?

Answer 37

Tumour specific antigens-an antigen that is the cause of the tumour such as mutation of TSGs or
oncogenes that leads to altered protein production. Found only on tumour cells.
• Tumour antigen: a protein with an abnormal structure caused by a mutation
• Tumour associated antigens- present on tumour cells and some normal cells. It is a mutation in a gene
unrelated to the tumour formation but causes the synthesis of abnormal proteins

Question 38

how doe cytotoxic T cells cause tumour cell apoptosis?

Answer 38

• they bind using their T cell receptor to the MHC-I on the cancer cell
• death receptor Fas Ligand induced apotosis

Question 39

how can tumour cells prevent T cell from killing them?

Answer 39

• (1) Cancer cells can stop the MHC antigen-processing complex and prevent loading of antigenic peptides
onto HLA/ MHC molecules, preventing the recognition of tumour antigens..
• (2) Tumour cells can upregulate the expression PDL1. PDL1 is a ligand expressed on tumour cells that
binds to an inhibitory receptor PD1 on T cells and deactives them.
• (3) Cancer cells can produce cytokines e.g. TGF-b, VEGF and IL-10 that cause immunosuppression by
recruiting T-regs and myeloid derived suppressor cells.

Question 40

what happenes when tumour-promoting effects our from macrophages?

Answer 40

-cancer cells release chemotactic factors that attract monocytes that >macrophages
tumour associated macrophages
-release angiogenic factors (VEG, IL-8)
-release metalloproteases that digest the extracellular matrix
-release mitogenic factors that promote tumour cells proliferation