Download Where are we heading? Unit 2:

Unit 2:
Unit 2: Introduction
Where are we heading?
Unit 1: What is cancer and why should we care?
Unit 2: What does it mean to be a 'normal' cell?
Unit 3: How does a normal cell become cancerous?
Unit 4: How does cancer make us sick?
Unit 5: How is cancer diagnosed and treated?
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Unit 2 focuses on how normal cells behave in
their tissue communities and in particular their
vulnerabilities to mutation.
Lesson 2.1 explores what kinds of normal cells are particularly
vulnerable to cancer, and why. Lesson 2.2 investigates how a cell
controls its ability to replicate and how this control is disrupted in
cancer. Lesson 2.3 asks the question of how all cells can have the
same DNA but perform different functions. Lesson 2.4 deals with the
process of cell death and uses the apoptosis game to illustrate how
it is disrupted in cancer. Lesson 2.5 grapples with the idea of a cell
as part of a tissue community, exploring how normal cells depend on
each other and how they become isolated during cancer.
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LESSON 2.1 WORKBOOK
Which cells are most vulnerable to
cancer, and why?
In the upcoming unit we will learn about how normal cells function, as a prelude
to learning about how these functions become abnormal during cancer. A useful
analogy is to think of each cell as a member of the community of cells that make
a tissue. In order for the tissue community to function properly each of its cell
members must communicate effectively with other community members in order
to perform its own specialized task. In this lesson we will define the cell community
we are most interested in – epithelial cells that are responsible for more than 80&
of all cancers.
MC Questions:
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The tissue community of cells
The complex function of the body as a whole is performed by individual organs, each of which plays a
particular role - such a respiration, digestion and reproduction. In turn each organ is composed of specific
components or tissues, which work as a community to perform that organ’s function. For example, the
respiratory system is composed of tissues that form the bronchi, which transfer air into and out of the body
cavity, and the lungs, where gas exchange into and out of the bloodstream take place. An organ’s tissues
are composed of individual cells each of which also has its own specialized function. But in order for the
tissue to function as a unit to drive organ function, each of the cells in the tissue must closely cooperate
with its neighbors. In the next few lessons we are going to focus on the tasks individual cells must perform
so that the community of cells as a whole can function. Just as individual members of any community are
born, make friends, grow up and get a job, and then grow old and die, so individual cells must accomplish
all of these tasks.
Wo r k b o o k
Lesson 2.1
1. Which is the smallest functional unit
of the body?
aa. System;
bb. Organ;
cc. Tissue; or
dd. Cell.
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LESSON READINGS
DEFINITIONS OF TERMS
Lumen – the inner space of a
tube.
Epithelial cells – closely packed
cells that separates the contents
of a lumen from the interior of the
body.
Parenchyma – the tissue of an
organ that is responsible for its
function.
Stroma – the connective tissue
framework of an organ that supports the epithelial layer of tissue.
Stromal cells – connective tissue cells and cells of the immune
system that are present in the
stroma that support epithelial cell
function.
For a complete list of defined
terms, see the Glossary.
Wo r k b o o k
Lesson 2.1
First of all we are going to identify a tissue community of cells to focus
on. The epithelium is a very good example. Our bodies are organized as a series of various “tubes” that connect organ to organ: For
example the digestive tract connects where we take food in via the
mouth to where waste is eliminated via the anus and passes through
the stomach and intestines, where food is absorbed. The blood and
lymph systems are a series of tubes that convey red and white blood
cells around the whole body. The liver and pancreas connect to each
other and to the intestines through tubes called bile ducts, that help
digest food. Finally the mammary glands in breasts secrete milk
through tubes called ducts.
Every organ’s system of tubes looks similar. The tube lining, called
Figure 1: Our body
the epithelium, is composed of a series of epithelial cells that are
can be viewed as a series
tightly attached to each other so they prevent substances within the
of tubes that move fluids
center of the tube (called its lumen) from leaking out. The epithelium
from organ to organ.
lining of the tubes performs different functions, depending on the
organ system it is associated with. For example some epithelia keep
the contents of the tube in the lumen – such as the bladder; some epithelia move contents out of the
lumen and into underlying blood vessels – such as the small intestine; and some epithelia move material
from the underlying tissue into the lumen of the tube – such as the mammary glands. In many cases an
organ’s tubes are its most important functional component. Because of this they are called the parenchyma of the organ (from the Greek ‘pour in’). Another important term in tube structure is the stroma
(from the Greek ‘mattress’) which is the supporting framework of the tissue underneath the epithelium that
helps keep the tubes intact.
Figure 2: Cross section of an epithelium in the esophagus. Epithelial cells
are in contact with the lumen of the
esophagus. They are supported by the
basement membrane and stroma, which
contains blood vessels.
We can therefore think of organs in general terms
having two tissue components: The epithelial
tube, consisting of individual epithelial cells tightly
attached to each other side to side to keep the
epithelium impermeable which often form the
functional parenchyma of the organ. Underneath
the epithelial lining is the supportive stroma, whose
main function is to support the epithelial tissue.
Within the stroma, blood vessels convey material to
and from the epithelial cells and provide nutrients
and signals for cell growth and survival. Lymph
vessels bring immune cells to the stroma to clear
MC Questions:
2. What are reasons that epithelial cells
are often the parenchyma tissue of
an organ? (Circle all correct.)
aa. They perform the function of the
organ.
bb. They are the fastest growing
cells.
cc. They are cells that form the
lining of the lumen.
dd. They are cells with best access
to blood and lymph.
3. What cells separate contents of the
lumen from the rest of the body?
aa. Basement membrane cells.
bb. Epithelial cells.
cc. Immune cells.
dd. Stromal Cells.
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LESSON READINGS
DEFINITIONS OF TERMS
Basement membrane – a thin
layer of connective tissue
underneath the epithelial tissue
layer.
Cuboidal epithelia – cubeshaped epithelial cells that
function for secretion.
Columnar epithelia – height
is much longer than their width.
These cells function for absorption of nutrients and secretion
and are found mostly in
the GI tract.
Transitional epithelia –
epithelial cells that can transition
in shape and size. These cells
are primarily found in the urinary
tract and prostate.
Wo r k b o o k
Lesson 2.1
away and dead cells and debris, as well as killing off pathogens that may have entered an organ.
MC Questions:
Separating the epithelial lining and the stroma is a layer of dense fibrous proteins called the basement
membrane. The basement membrane does not have the same structure as a cell membrane, rather
it is a dense layer of fibrous proteins that acts like ‘insulation’ for the epithelial lining of the tube to make
absolutely sure that the epithelium stays intact. The basement membrane is critically important for cancer,
as we will see.
4. Which of the following cell types
would likely be present in a tumor of
the mammary gland?
aa. Cuboidal epithelia;
bb. Columnar epithelia;
cc. Squamous epithelia; or
dd. Transitional epithelia.
Different epithelial cells have different functions
As we saw before, different organ tubes have
different functions, and this is reflected in
differences in the epithelial cells that line the
tubes. Organs like the stomach that secrete
gastric acid have different types of epithelia
lined than organs like the small intestine that
absorb nutrients. The skin too, has an epithelial lining, although in this case the ‘lumen’ is
the entire outside world. We can distinguish
four different kinds of epithelial cells:
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Figure 3: Cartoon depiction of four types of
epithelial cells. Each type has a distinct function.
■■ Cuboidal epithelia are shaped like
cubes. They are specialized for secretion so they are commonly found in organs where secretion is
important, such as salivary glands (saliva) and mammary glands (milk).
■■ Columnar epithelia are elongated and tightly packed. They are specialized for absorption and
secretion and can also handle harsh chemicals and mechanical stress so they are mostly found in
the digestive tract.
■■ Transitional epithelia vary in shape between cuboid and columnar. They are specialized to be
stretchy without breaking so they are mostly found in organs that need to expand and contract
like the urinary bladder, and gland ducts of the prostate. They often occur in layers to give more
mechanical strength.
■■ Squamous epithelia are flat and look like fish scales (squamous is Latin for ‘scale’). They are
specialized to be protective and are found where protection from mechanical forces is needed, such
as on the surface of the skin or lining blood vessels and the abdominal cavity Skin is composed of
squamous epithelium that protects us from the environment. Other squamous cells are found on
surfaces not typically exposed to the environment, such as blood vessels or the linings of internal
body cavities.
5. Which of the following cell types
would likely be found in a tumor of
the GI tract?
aa. Cuboidal epithelia;
bb. Columnar epithelia;
cc. Squamous epithelia; or
dd. Transitional epithelia.
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LESSON READINGS
Epithelial cells that are frequently exposed to stress or damage often form multiple layers, which allows for
cells on the outside to die without damaging inner lining of the tube. Multiple layered epithelia are found
in skin, hair, and nails, as well as in glands and organs that need to expand and contract. In contrast
epithelia involved in absorption in the digestive tract are specifically organized to take a substance up at
the lumen side, transport the material through the cell and release it at the other side (cells that secrete do
the opposite). These cells usually exist in a single layer to maintain the direction of transport.
Why epithelial cells are important in cancer.
DEFINITIONS OF TERMS
Squamous epithelia – flat,
scale-like, epithelial cells whose
chief function is protection from
the environment
In theory, any cell can develop into a tumor or cancer, but epithelial cell cancers are responsible for ~80%
of cancer-related deaths in the Western world (and ~70% in the developing world). Given what we now
know about how important epithelial cells are to the function of nearly every organ in the body, this should
not be at all surprising. If we describe a cancer by the type of cell that is affected, rather than the organ
the cancer derives from, it is clear why epithelial cell cancers are so common. This raises another point
also: It has now become clear that cancer of transitional epithelia in say kidney and prostate will have
a more in common with each other than a cancer of kidney epithelia compared with a cancer of kidney
stroma. As we understand more about how communities of cells in tissues are abnormal in cancers we
are moving away from describing cancers by the organ they occur in, to the tissue affected: carcinomas,
if the cancer originated from a squamous epithelial cell, or adenocarcinoma, if the cancer originated from
a columnar, cuboid or transitional epithelial cell.
Not all cancers originate from epithelial cells. The other major types of tumors originate from non-epithelial cells are:
Proliferate – the act of cells
dividing
■■ Sarcomas - these tumors originate from the cells found in stroma.
■■ Leukemias/Lymphomas – these tumors originate from white blood cells and cells of lymph nodes.
■■ Neuroectodermal tumors – these tumors originate from components of the nervous system.
■■ Melanomas – these tumors originate from the pigmented cells of the skin.
■■ Small-cell carcinomas – these tumors originate from a subset of cells found in the lung and cervix.
Wo r k b o o k
Lesson 2.1
Even this type of classification has problems because it is quite common for a single tumor to be
composed of multiple types of carcinomas. Furthermore an organ may contain both carcinomas and
sarcomas. For instance, more than 90% of all prostate cancers are adenocarcinoma, but the other 10%
can be other types of carcinomas or even sarcomas.
MC Questions:
6. Which of the following types of
tumors would be found in the
prostate gland? (Circle all correct.)
aa. Adenocarcinoma.
bb. Carcinoma.
cc. Melanoma.
dd. Sarcoma.
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7. Which of the following is most useful
to describe a cancer? (Circle all
correct.)
aa. The cell the cancer originates
from.
bb. The tissue the cancer originates
from.
cc. The organ the cancer originates
from.
dd. The system that cancer
originates from.
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LESSON READINGS
DEFINITIONS OF TERMS
Benign – a tumor located to the
epithelial cell layer
Malignant – a tumor that has
broken through the basement
membrane and entered the
stroma.
Carcinoma – general term for a
cancer of an epithelial cell.
Squamous cell carcinoma –
cancer of squamous epithelia
Adenocarcinoma – cancer of
columnar, cuboid, or transitional
epithelial cells.
Sarcoma – cancer of cells from
the stroma
Hyperproliferation – when cells
proliferate at abnormally high
levels.
Wo r k b o o k
Lesson 2.1
Why do most tumors originate in epithelial
cells? Again we need to look at epithelia
location and function. As the barrier
between the outside world and the inside
they are the first line of defense against
damaging environmental factors. We
learned in the Infectious Disease module
that epithelia are exposed to infectious
agents, like viruses and bacteria. They are
also damaged by physical irritation, chemiFigure 4: Cells that proliferate normally have
cals and even hormones. When epithelial
a defined shape and size. Hyperproliferating
cells get damaged and die, others must
cells grow rapidly and look abnormal.
grow to replace them. The more frequently
they are damaged the more rapid the
replication. The more a cell proliferates, the more likely it is to acquire mutations that will lead to tumor
formation. This phenomenon is called hyperproliferation. Another name for a substance that damages a
cell making it hyperproliferate and leading to tumor formation is a carcinogen.
Tumors at the interface between the outside world and the body are, as epithelial tumors are, more likely
to be detected than tumors buried within the stroma, which may not produce symptoms until they are very
large. In contrast, carcinomas seen on the skin, or in the lung, or GI tract will produce obvious symptoms. It is possible that cancers exist in other parts of the body that we never observe and never cause
symptoms of disease. As we will see later on, the cell(s) that form the tumor plays an important part in how
a tumor develops, what type of cancer will be produced, and what the disease outcome of that cancer will
be.
MC Questions:
8. Why do most cancers originate from
epithelial cells? (Circle all correct.)
aa. Epithelial cells are the most
exposed to carcinogens.
bb. Epithelial cells hyperproliferate
more than other cells.
cc. Epithelial cells break through
basement membrane.
dd. Epithelial cells are cells most
likely to produce symptoms.
9. Which of the following is the step
that initially differentiates a cancer
from a tumor?
aa. Hyperproliferation of cells;
bb. Formation of a tumor;
cc. Tumor breaks through basement
membrane; or
dd. Tumor enters blood stream.
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STUDENT RESPONSES
Describe 2 reasons why you think 80% of cancers originate from epithelial cells.
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Remember to identify your
sources
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Wo r k b o o k
Lesson 2.1
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TERMS
TERM
For a complete list of defined
terms, see the Glossary.
Wo r k b o o k
Lesson 2.1
DEFINITION
Adenocarcinoma
Cancer of columnar, cuboid, or transitional epithelial cells.
Basement membrane
A thin layer of connective tissue that underlines the epithelial tissue layer.
Carcinoma
General term for a cancer of the epithelial cell.
Columnar epithelia
Cells whose height is much longer than their width. These cells function for absorption of nutrients and
secretion and are found mostly in the GI tract.
Cuboidal epithelia
Cube-shaped epithelial cells that function for secretion.
Epithelial cells
One of many closely packed cells that separates the contents of a lumen from the rest of the body.
Hyperproliferation
When cells proliferate at abnormally high levels.
Lumen
The inner space of a cavity, vessel, intestine, or other tube.
Parenchyma
The tissue of the organ that is responsible for the function of that organ.
Proliferate
The act of cells dividing.
Sarcoma
Cancer of cells from the stroma.
Squamous epithelia
Flat, scale-like, epithelial cells whose chief function is protection from the environment.
Stroma
The connective tissue framework of an organ that supports the epithelial layer of tissue.
Stromal cells
Connective tissue cells and cells of the immune system that are present in the stroma that support epithelial
cell function.
Transitional epithelia
Epithelial cells that can transition in shape and size. These cells are primarily found in the urinary tract and
prostate.
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