Transcript Cancer

BIOL 445 Cancer Biology
Spring 2015
Mark Peifer and Bob Duronio
BIOL 445
In Bio 445 we combine
the approaches of Bio 202 + Bio 205
with the current scientific literature
to study the family of diseases
known as cancer
You may not believe it but by the end of the semester
This will make sense!
Hanahan and Weinberg, Cell 100:57-70 (2000)
Virtually everything you’ll need is found at:
http://www.bio.unc.edu/Courses/2015Spring/Biol445/
It’s a REALLY good idea to
look through this carefully THIS WEEK
AND
Check back frequently for updates or changes
We will also us the course Sakai site for online quizzes,
Blogs, and as a place for a discussion forum
BIOL 445
Textbooks
-The Biology of Cancer by Robert Weinberg 2nd Edition
What are you responsible for?
- Lectures (attendance AND participation)
- Papers and assigned textbook reading(on website)
-Your project- literature search and presentation
Grading
- Exams (20% X 2 midterms + 25% final) = 75
- Presentations = 15
- Classroom discussion, online and in-class
evaluations = 10
Your Project
- Choose a topic
- Read the posted review paper
- Do a thorough literature research, including
primary data on the gene and the disease
- Make a poster and present it to your peers
- The final exam will cover ALL posters
Cancer:
a family of diseases
caused by our own cells gone wrong
Cancer is number 2
and rising relative to heart disease!
CDC
But as we’ll see, Cancer is
not one disease, its many
ONS=Other nervous system.
Source: American Cancer Society, 2009.
Lifetime Probability of Developing Cancer,
By Site, Men, US, 2007-2009
Site
All sites
Prostate
Risk
1 in 2
1 in 6
Lung and bronchus
1 in 13
Colon and rectum
1 in 19
Urinary bladder
1 in 26
Non-Hodgkin lymphoma
1 in 43
Melanoma
1 in 40
Kidney
1 in 49
Leukemia
1 in 63
Oral Cavity
1 in 67
Stomach
1 in 92
Source: ACS http://www.cancer.org/Cancer/CancerBasics/lifetime-probability-of-developing-or-dying-from-cancer
Lifetime Probability of Developing Cancer,
By Site, Women, US, 2007-2009
Site
Risk
All sites
Breast
1 in 3
1 in 8
Lung & bronchus
1 in 16
Colon & rectum
1 in 21
Uterine corpus
1 in 38
Non-Hodgkin lymphoma
1 in 52
Melanoma
1 in 63
Pancreas
1 in 69
Ovary
1 in 72
Kidney
1 in 83
Urinary bladder
1 in 87
Source: ACS http://www.cancer.org/Cancer/CancerBasics/lifetime-probability-of-developing-or-dying-from-cancer
We are making progress, however!!
March 28.2012
Cancer is NOT an infectious disease
Cancer is NOT an infectious disease
Instead it illustrates the challenge of
understanding how genetics and the
environment combine to cause disease
To understand what goes WRONG,
we need to understand
how things normally go right
Cells within a tissue are normally highly
organized and tightly regulated
e.g. intestine
e.g. skin
Cancer: an aberration of normal development
Cancer cells exhibit behaviors found
in normal cells during development,
differentiation, and homeostasis
Cancer: an aberration of normal development
Cancer cells exhibit behaviors found
in normal cells during development,
differentiation, and homeostasis
However, cancer cells put together suites
Of cell behaviors in problematic ways
And do so out of normal regulatory controls
All cancers have a genetic basis-they are diseases of our own cells gone wrong
Sometimes inherited mutations play a role.
e.g., Familial adenomatous polyposis (FAP)
=inherited predisposition to colon cancer
However, most cases result from the
Slow accumulation of
Somatic mutations
Cancer results
from a
series of mutations,
each further
altering the cell
Lodish et al.
Fig. 24-6
The last two years
has seen a revolution
in our knowledge of
the full array of mutations
in many tumor types
Properties of Cancer Cells
Most normal cells have a limited
potential to divide
senescent cells
Normal stem cells can divide
indefinitely, but under tight control
Differentiated cells
Self-renewing
stem cell
Properties of Cancer Cells
Cancer cells are "immortalized”,
just like stem cells, but w/o control
Differentiated cells
Self-renewing
stem cell
Cancer cell
Most Normal cells
differentiate
But stem cells
do NOT
differentiate
Like normal stem cells
Cancer cells do not differentiate
tumor
Most normal cells stop proliferating
under contact inhibition
in vitro
Figure 20-29 Molecular Biology of the Cell (© Garland Science 2008)
in vivo
Cancer cells are not under contact inhibition
Figure 20-29 Molecular Biology of the Cell (© Garland Science 2008)
However cells of early embryos
also lack contact inhibition,
but then gain it at the
mid-blastula transition
Normal
“Transformed”
Cancer cells have
alterations in
cell adhesion
and the cytoskeleton
These changes in
cell shape and behavior
are shared by
many migrating cells,
including those that
Look outmigrate into wound sites Here I
Come!
Cell from:
www.basic.northwestern.edu/ g-buehler/micropl.jpg
Late stage cancer cells are invasive
normal
tissue
invasive
tumor
Figure 20-17 Molecular Biology of the Cell (© Garland Science 2008)
Normal cells can be invasive at the
right time and place
Seward Hung
Normal cells that are
starved for O2 Induce Angiogenesis
Can’t breath!
Send Blood vessels
Consequences
1. Nutrients and oxygen are supplied to the tissue
Cancer Cells also Induce Angiogenesis
Consequences
1. Nutrients and oxygen are supplied to the tumor
2. New blood vessels provide as easy way out
Some properties of Cancer Cells
involve evading normal behaviors that
limit growth and prevent damage
Normal cells may undergo
apoptosis
as part of a
developmental program
when cells become
“dangerous” (e.g. DNA
damage)
Properties of Cancer Cells
Cancer cells escape apoptosis
blue cells =
breast cancer cells
yellow cells =
apoptotic cells
Dave McCarthy and Annie Cavanagh
Cancer: an aberration of normal development
Cancer cells exhibit behaviors found
in normal cells during development,
differentiation, and homeostasis
However, cancer cells put together suites
Of cell behaviors in problematic ways
And do so out of normal regulatory controls
Properties of Cancer Cells
- Cancer cells are "immortalized”
- Cancer cells do not form differentiated tissues
- Cancer cells are not under contact inhibition
- Cancer cells are invasive
- Cancer cells escape apoptosis
This Lecture
- Properties of cancer cells
- Tumor progression
- What causes cancer?
- Accumulation of mutations
Cancer develops through gradual changes
in cell morphology and properties
Figure 20-9 Molecular Biology of the Cell (© Garland Science 2008)
Tumor Progression
Tumor = abnormal growth of solid tissue
benign- self
contained
malignantinvasive
Metastasis is a difficult and dangerous process
both for the tumor cell and the host!
Figure 20-17 Molecular Biology of the Cell (© Garland Science 2008)
This is what you do NOT want
Cellular changes required for metastasis
Figure 20-44 Molecular Biology of the Cell (© Garland Science 2008)
This Lecture
- Properties of cancer cells
- Tumor progression
- What causes cancer?
- Accumulation of mutations
What Causes Cancer?
Cancer : Accumulation of Mutations
-
Random mutations (mistakes at the assembly line
or induced by environment)
- Inherited mutations (pre-disposition)
- Viral infections (cervical cancer and a few rare types)
The first association between
occupation and cancer
Percivall Pott found that chimney sweeps show
substantially higher rates of skin cancer
British chimney sweeps
didn’t do anything about it
Danish chimney sweeps :
a daily bath after work
Result: significantly lower rates of skin cancer
amongst Danish versus British chimney sweeps,
even a century later
A happy Danish chimney sweep
at work
with the family
Yamagiwa took it one step further
Coal tar condensates induced
skin carcinoma in rabbits
Chemicals can directly
induce cancer
Cancer can be studied
in the lab
Yamagiwa
Figure 2.21b The Biology of Cancer (© Garland Science 2007)
Carcinogens = agents that contribute to
the formation of a tumor
Figure 20-20b Molecular Biology of the Cell (© Garland Science 2008)
Can YOU see the trend in the data?
This Lecture
- Properties of cancer cells
- Tumor progression
- What causes cancer?
- Accumulation of mutations
Cancer often starts with a
single mutation
However
One mutation is not enough !!
Heard of
natural selection?
The fact that cancer is
a multi-step process is
reflected in correlation
between age and
incidence of cancers
Figure 20-7 Molecular Biology of the Cell (© Garland Science 2008)
Cancer cells also accumulate
chromosomal abnormalities,
especially late in the process
Figure 20-13 Molecular Biology of the Cell (© Garland Science 2008)