CELREGULATIE IN BEELD SAMENVATTING
HOORCOLLEGE 1 – 3/2/2025
LECTURE 1 - THE NATURE OF CANCER
Benign vs malignant tumors
- Benign: tumors that grow without invading adjacent tissues
→ Benign tumors can cause problems: hyperthyroidism and acromegaly
- Malignant: tumors that invade nearby tissues and spawn metastases
Tumors arise from specialized cell types
Tumors arise from epithelial tissues:
- Epithelia: sheets of cells that line the walls of the cavities (lungs, digestion…)
and channels or cover the body (skin)
- Basement membrane (basal lamina): is made of extracellular matrix (ECM)
(DUS basal lamina bestaat niet uit cellen) and separates the epithelial cells
from the underlying layer of supporting connective tissue cells (stroma)
Carcinomas are originated from the epithelia
There are two major types of epithelial-origin cancers (TENTAMEN VRAAG
OVER VERSCHIL TUSSEN DEZE 2 CARCINOMAS)
- Squamous cell carcinomas → originated from the protective layers in the
epithelium
- Adenocarcinomas → originated from cells that produce (secrete) stuff
(hormones)
BOTH carcinomas are originated from the epithelia
Non-epithalial cancers 1: connective-tissue – sarcomas
- Sarcomas derive from cells from connective tissues; fibroblast, secretory cells,
fat cells, osteoblast, myocytes (muscle forming cells)
Non-epithelial cancers 2: hematopoietic (blood-forming) tissues
- Hematopoietic are originated from blood forming cells/ tissues
→ Hematopoietic can originated from pre-cursors of erythrocytes (red blood
cells), antibody-secreting (plasma) cells, T and B lymphocytes
- Leukemia (white blood) is a type of cancer that is originated from changes in
the pre-cursors of blood cells
→ Leukemia is a cancer that moves through circulation
- Lymphomas are malignant B or T lymphocytes that originated from changes
in the pre-cursors of blood cells
→ Lymphomas aggregate (cluster) and form solid tumors
Non-epithelial cancers 3: originating from nervous system
- Gliomas, glioblastomas, neuroblastomas
Not all tumors can be easily classified
- Some tumors (and normal cells) undergo transdifferentiation (switch from
origination → move from one different lineage, or phenotype, to another)
→ Epithelial - to mesenchymal transition (EMT): epithelial cancers change
shape and gene expression programs that resemble nearby stromal cells
1
, - Teratomas (usually benign) arise from germ cell (egg and sperm) precursors
that persist at wrong sites in the developing fetus, retaining the ability to
generate most tissues → Teratomas can damage function of organs
→ Teratomas are wild-type (contain no mutation/ are not cancerous)
- Tumors that will lose tissue-specificity (dedifferentiation); process of gene
expression and phenotype changes so that cells stop resembling the tissues
of origin (anaplastic)
Cancers develop progressively
- Hyperplastic growth: in the normal tissue there will be excessive number of
cells → ratio of different types of cells will be disturbed
- Metaplastic growth: normally present tissue is replaced by invading cells from
a nearby tissue
- In Barretts esophagus: the squamous cells are replaced by secretory cells
These changes are NOT malignant, but they increase the risk for malignant cancers
- Dysplasia: transitional state between benign and malignant growth; increased
replicating cells, ratio of different types of cells is disturbed
- Adenomas, polyps, papillomas and skin warts contain all cell types of normal
epithelial tissue, but are greatly expanded (= in between state; NOT malignant
but can become this)
- Neoplasm (new tissue): cells have invaded the underlying tissues (=
carcinoma cells break through the basement membrane and invade into
adjacent stroma)
But: tumor progression (normal → hyperplastic → dysplastic → neoplastic →
metastatic) is only suggestive and not universal (steps can be skipped or tumors
cannot come any further than certain steps)
Are tumors monoclonal?
Do tumor cells descend from a single cell or from a large
cohort? → SINGLE CELL
Tumors are monoclonal in origin; this means that at
some point there is a single cell that started the cascade
of events when forming a tumor.
Tumors are not monoclonal; this means that all the cells
in the tumor are NOT identical, they have different
mutations.
SUMMARY:
- Tumors are monoclonal if you look at the cell of origin, but later there will be
different populations of cell in the tumor (=clone)
- Genetic heterogeneity of the tumor may mask its monoclonal origin, since
many of the genetic markers in descendant cells will be present only in
specific subpopulations of cells within the tumor mass
2
,Cancers exhibit altered energy metabolism
Normal cells in aerobic condition (enough oxygen) will use glycolysis in the cytosol to
break down glucose into pyruvate, which is then broken down in mitochondria into
CO2 → gives energy (ATP)
Warburg effect
Under anaerobic conditions (low oxygen) cells still need energy and will use a
different path. Cells will use glycolysis, reduce pyruvate to lactate and secrete the
lactate → gives energy (ATP), but is less efficient because less energy is produced
Cancers are often oxygen deprived
Even if cancer cells have enough oxygen, they will often use the glycolysis which
makes lactate to produce energy = Warburg effect
Why the Warburg effect?
- Cancer cells need energy, but also metabolites and under low oxygen
conditions the glycolysis produces more metabolites
- Because of the inefficient way of energy production of cancer cells, they will
need more glucose. Solid tumors will take up a lot of glucose.
Cancer frequencies vary between different populations
- Some cancers are caused by random, unavoidable ‘accidents’ which occur
with comparable frequencies in various populations
- Two obvious contributing factors: heredity and environment
- Cancers can be caused by external factors → environment plays a role
SUMMARY
- Cancer is not always malignant, metastases underlie almost all fatal outcomes
- Most cancers arise from epithelial tissues
- Cancer develops progressively
- Cancers are monoclonal (originate from a single cell)
- Both hereditary and environmental factors determine cancer risk
LECTURE 2 - VIRUSES, ONCOGENES AND GROWTH FACTORS
What are viruses?
Living organisms that will use the host to replicate their genomes and to
produce extra proteins. Their proteins will produce new viral particles that
will be secreted by the cell producing more viruses.
TENTAMENVRAAG PERMISSIVE HOST AND NON-PERMISSIVE HOST
- Permissive hosts (allowing virus replication)
→ Host cells quickly killed the virus; tumorigenic transformation will never
occur is the host cells are killed
- Non-permissive hosts (not allowing virus replication)
→ Transformed cells; host cells have defense mechanisms and will be
protected from replicating viruses. Therefore, host cells will transform at low
frequency (tumorigenic transformation)
Permissive host have an advantage, because when the cell dies the tumor cannot
grow → tumorigenic transformation of viruses is prevented in the organism
3
, Some viruses integrate their DNA into the host genome
How do tumorigenic viruses cause tumor growth?
Viral particles can insert their own genetic material into the genetic material of the
host (=recombination) and then new viruses will be produced.
Some viruses persist episomally (outside of host genome)
- Some viruses will NOT integrate, but can catch on the chromosomes of the
host and ride to the next generation
Some RNA viruses (retroviruses) use reverse transcription to integrate their genetic
material into DNA of the host cell
Some virus kidnap and exploit host genes
The ALV virus infected a chicken cell, and the
virus was integrated next to the c-src gene (healty
gene). During transcription the c-src gene was
accidentally copied onto the viral DNA. The host
gene was copied into the viral genome. Now the
virus is called RSV virus carrying the v-src gene.
TENTAMEN TERM
Oncogene: a gene with a potential to become oncogenic → to contribute
transformation of normal cells into tumor cells
Conclusions:
- Existing normal genes could be oncogenic
→ Viruses copy the host gene (healthy gene) and when reinfecting an
organism this gene could be oncogenic
- Viruses can be used as vectors to deliver foreign DNA into cells
Viruses are important carcinogens
- Many cancers world-wide are caused by infectious agents (HPV, Hep B/C)
Are all cancers induced by viruses?
- Cancer does not propagate between humans
- Non-biological agents can be oncogenic (chemicals, X-ray)
Mutation as drivers of transformation
- Oncogenes act across species – because they are evolutionarily conserved
- The same oncogenes were found responsible for virus- and mutation-driven
transformation
- The genes are the target of the oncogenic transformation
4
HOORCOLLEGE 1 – 3/2/2025
LECTURE 1 - THE NATURE OF CANCER
Benign vs malignant tumors
- Benign: tumors that grow without invading adjacent tissues
→ Benign tumors can cause problems: hyperthyroidism and acromegaly
- Malignant: tumors that invade nearby tissues and spawn metastases
Tumors arise from specialized cell types
Tumors arise from epithelial tissues:
- Epithelia: sheets of cells that line the walls of the cavities (lungs, digestion…)
and channels or cover the body (skin)
- Basement membrane (basal lamina): is made of extracellular matrix (ECM)
(DUS basal lamina bestaat niet uit cellen) and separates the epithelial cells
from the underlying layer of supporting connective tissue cells (stroma)
Carcinomas are originated from the epithelia
There are two major types of epithelial-origin cancers (TENTAMEN VRAAG
OVER VERSCHIL TUSSEN DEZE 2 CARCINOMAS)
- Squamous cell carcinomas → originated from the protective layers in the
epithelium
- Adenocarcinomas → originated from cells that produce (secrete) stuff
(hormones)
BOTH carcinomas are originated from the epithelia
Non-epithalial cancers 1: connective-tissue – sarcomas
- Sarcomas derive from cells from connective tissues; fibroblast, secretory cells,
fat cells, osteoblast, myocytes (muscle forming cells)
Non-epithelial cancers 2: hematopoietic (blood-forming) tissues
- Hematopoietic are originated from blood forming cells/ tissues
→ Hematopoietic can originated from pre-cursors of erythrocytes (red blood
cells), antibody-secreting (plasma) cells, T and B lymphocytes
- Leukemia (white blood) is a type of cancer that is originated from changes in
the pre-cursors of blood cells
→ Leukemia is a cancer that moves through circulation
- Lymphomas are malignant B or T lymphocytes that originated from changes
in the pre-cursors of blood cells
→ Lymphomas aggregate (cluster) and form solid tumors
Non-epithelial cancers 3: originating from nervous system
- Gliomas, glioblastomas, neuroblastomas
Not all tumors can be easily classified
- Some tumors (and normal cells) undergo transdifferentiation (switch from
origination → move from one different lineage, or phenotype, to another)
→ Epithelial - to mesenchymal transition (EMT): epithelial cancers change
shape and gene expression programs that resemble nearby stromal cells
1
, - Teratomas (usually benign) arise from germ cell (egg and sperm) precursors
that persist at wrong sites in the developing fetus, retaining the ability to
generate most tissues → Teratomas can damage function of organs
→ Teratomas are wild-type (contain no mutation/ are not cancerous)
- Tumors that will lose tissue-specificity (dedifferentiation); process of gene
expression and phenotype changes so that cells stop resembling the tissues
of origin (anaplastic)
Cancers develop progressively
- Hyperplastic growth: in the normal tissue there will be excessive number of
cells → ratio of different types of cells will be disturbed
- Metaplastic growth: normally present tissue is replaced by invading cells from
a nearby tissue
- In Barretts esophagus: the squamous cells are replaced by secretory cells
These changes are NOT malignant, but they increase the risk for malignant cancers
- Dysplasia: transitional state between benign and malignant growth; increased
replicating cells, ratio of different types of cells is disturbed
- Adenomas, polyps, papillomas and skin warts contain all cell types of normal
epithelial tissue, but are greatly expanded (= in between state; NOT malignant
but can become this)
- Neoplasm (new tissue): cells have invaded the underlying tissues (=
carcinoma cells break through the basement membrane and invade into
adjacent stroma)
But: tumor progression (normal → hyperplastic → dysplastic → neoplastic →
metastatic) is only suggestive and not universal (steps can be skipped or tumors
cannot come any further than certain steps)
Are tumors monoclonal?
Do tumor cells descend from a single cell or from a large
cohort? → SINGLE CELL
Tumors are monoclonal in origin; this means that at
some point there is a single cell that started the cascade
of events when forming a tumor.
Tumors are not monoclonal; this means that all the cells
in the tumor are NOT identical, they have different
mutations.
SUMMARY:
- Tumors are monoclonal if you look at the cell of origin, but later there will be
different populations of cell in the tumor (=clone)
- Genetic heterogeneity of the tumor may mask its monoclonal origin, since
many of the genetic markers in descendant cells will be present only in
specific subpopulations of cells within the tumor mass
2
,Cancers exhibit altered energy metabolism
Normal cells in aerobic condition (enough oxygen) will use glycolysis in the cytosol to
break down glucose into pyruvate, which is then broken down in mitochondria into
CO2 → gives energy (ATP)
Warburg effect
Under anaerobic conditions (low oxygen) cells still need energy and will use a
different path. Cells will use glycolysis, reduce pyruvate to lactate and secrete the
lactate → gives energy (ATP), but is less efficient because less energy is produced
Cancers are often oxygen deprived
Even if cancer cells have enough oxygen, they will often use the glycolysis which
makes lactate to produce energy = Warburg effect
Why the Warburg effect?
- Cancer cells need energy, but also metabolites and under low oxygen
conditions the glycolysis produces more metabolites
- Because of the inefficient way of energy production of cancer cells, they will
need more glucose. Solid tumors will take up a lot of glucose.
Cancer frequencies vary between different populations
- Some cancers are caused by random, unavoidable ‘accidents’ which occur
with comparable frequencies in various populations
- Two obvious contributing factors: heredity and environment
- Cancers can be caused by external factors → environment plays a role
SUMMARY
- Cancer is not always malignant, metastases underlie almost all fatal outcomes
- Most cancers arise from epithelial tissues
- Cancer develops progressively
- Cancers are monoclonal (originate from a single cell)
- Both hereditary and environmental factors determine cancer risk
LECTURE 2 - VIRUSES, ONCOGENES AND GROWTH FACTORS
What are viruses?
Living organisms that will use the host to replicate their genomes and to
produce extra proteins. Their proteins will produce new viral particles that
will be secreted by the cell producing more viruses.
TENTAMENVRAAG PERMISSIVE HOST AND NON-PERMISSIVE HOST
- Permissive hosts (allowing virus replication)
→ Host cells quickly killed the virus; tumorigenic transformation will never
occur is the host cells are killed
- Non-permissive hosts (not allowing virus replication)
→ Transformed cells; host cells have defense mechanisms and will be
protected from replicating viruses. Therefore, host cells will transform at low
frequency (tumorigenic transformation)
Permissive host have an advantage, because when the cell dies the tumor cannot
grow → tumorigenic transformation of viruses is prevented in the organism
3
, Some viruses integrate their DNA into the host genome
How do tumorigenic viruses cause tumor growth?
Viral particles can insert their own genetic material into the genetic material of the
host (=recombination) and then new viruses will be produced.
Some viruses persist episomally (outside of host genome)
- Some viruses will NOT integrate, but can catch on the chromosomes of the
host and ride to the next generation
Some RNA viruses (retroviruses) use reverse transcription to integrate their genetic
material into DNA of the host cell
Some virus kidnap and exploit host genes
The ALV virus infected a chicken cell, and the
virus was integrated next to the c-src gene (healty
gene). During transcription the c-src gene was
accidentally copied onto the viral DNA. The host
gene was copied into the viral genome. Now the
virus is called RSV virus carrying the v-src gene.
TENTAMEN TERM
Oncogene: a gene with a potential to become oncogenic → to contribute
transformation of normal cells into tumor cells
Conclusions:
- Existing normal genes could be oncogenic
→ Viruses copy the host gene (healthy gene) and when reinfecting an
organism this gene could be oncogenic
- Viruses can be used as vectors to deliver foreign DNA into cells
Viruses are important carcinogens
- Many cancers world-wide are caused by infectious agents (HPV, Hep B/C)
Are all cancers induced by viruses?
- Cancer does not propagate between humans
- Non-biological agents can be oncogenic (chemicals, X-ray)
Mutation as drivers of transformation
- Oncogenes act across species – because they are evolutionarily conserved
- The same oncogenes were found responsible for virus- and mutation-driven
transformation
- The genes are the target of the oncogenic transformation
4
