Week 3 - Physiology of Cancer: Explain Cancer, Cell Division, & Genes

 Week 3 - Physiology of Cancer: Explain
Cancer, Cell Division, & Genes

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DNAKeep our central discussion question in mind as we explore some of the science behind this scenario: Your friend tells you she recently had genetic testing done, and her doctor said she “inherited a single mutation in a gene that is connected to breast cancer.”  Your friend is unsure what this means and is worried she will definitely get breast cancer later in life.

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In reality, the quote from the doctor above is very vaguely written and hopefully no patient would ever get this information without much additional context and counseling!  We will use the vague nature of this quote to break down cancer into pieces and explore its physiology.  In a way, we will address the doctor's quote in reverse order.  The final part of the quote mentions "breast cancer," so first we will try to ensure we're speaking a common language about what cancer is.

Scratched KneeOne thing we should start with is to note that cancer is a disease of cell division.  White blood cell surrounded by red blood cellsThat's not to say cell division is a bad thing!  Cell division is essential for us to grow, heal wounds, and replace worn out cells.  In fact, one of the main reasons we tend to experience a higher risk of disease and injury as we age is that our cells stop dividing as efficiently.  For example, you can imagine how poorly dividing white blood cells would cause increased risk for infection, which is a characteristic of aging.  So you can see how it's critical to have proper and well timed cell division.  Inappropriate cell division in either direction can lead to disease.

Physiologists track a cell's status and chances of dividing by referring to the cell cycle.  The cell cycle is often represented as a circle and has abbreviations to represent what the cell is doing in different stages of its life.  image.pngThe G1, S, and G2 phases are all considered part of interphase.  Cells spend most of their lives in interphase.  The "G" phases are stages where the cell is growing, producing proteins, and generally performing whatever functions it's assigned with in the body.  The "S" phase refers to "synthesis" of DNA.  That is, the cell replicates its DNA in the S phase.  The smallest piece of this diagram, the "M" phase, refers to "mitosis" when the cell separates the copies of its DNA and divides.  Neurons and Muscle CellsThis is only a small part of the cell cycle, but is crucial for the reasons described above!  (growth, healing, replacement of cells, etc.)  If you look closely at this diagram, you'll also see that some cells exit the cell cycle entirely and remain in a relatively permanent state of "G0."  Muscle cells and neurons are examples of cells that typically do not divide (or only divide relatively rarely) after we're born.  Those cells would be in the G0 phase.

As we mentioned, a slowdown in the cell cycle can cause symptoms of aging.  On the other hand, an unnecessary acceleration of the cell cycle can result in cancer.  Click here

Links to an external site. and view the video on that page to see some of the steps in cancer development.  Note especially the roles of angiogenesis and metastasis.

Why is angiogenesis necessary for cancer growth?

Why is metastasis necessary for aggressive cancer (i.e., why would cancer be more easily treatable if metastasis did not happen)?

Most common forms of cancer, including breast, prostate, lung, colon, and bladderIt might be easy to wonder...if cancer gives us more cells, why isn't that a good thing?  For example, wouldn't more white blood cells just give us a greater ability to fight infection?  The problem is that cancer cells are abnormal cells that no longer perform their proper functions.  Instead of having a larger supply of helpful cells, cancer gives us a larger supply of useless cells that only serve to take space and resources away from properly functioning cells around them.  The diagram to the right shows the most common types of cancer in men and women.  You'll notice some prominent organs are missing from the lists!  For example, muscles, heart, and brain.  While it's possible to have cancers of muscle cells and neurons, those cancers are quite rare.  This makes sense if you think about the discussion above regarding the cell cycle.  Muscle cells and neurons are typically in the G0 phase, meaning they do not often divide.  That makes it unlikely that they would start dividing out of control.  The most common cancers are in cells that are already prone to dividing.

cells connected by adherens junctions and desmosomesThere's one more factor related to the risk for aggressive cancer that connects with our learning goals.  Many cells are physically connected to one another via proteins.  These connections are called cell junctions. Two examples of cell junctions are adherens junctions and desmosomes (see picture to left).  Recall that metastasis was an important step in the risk for aggressive cancer.

If cells are connected by lots of adherens junctions and desmosomes, how might that impact their likelihood of metastasizing?

It turns out this is a major area of cancer research.  It's difficult for cells to metastasize (i.e., spread) if they are physically connected to one location.  They just can't physically get away!  As a result, many researchers believe it is necessary for cancer cells to lose their adherens junctions and desmosomes in order for those cancers to become aggressive.  Some examples of this are shown in the diagrams below, which come from recent cancer research papers.

diagram showing loss of junctions as critical to cancer spread

The above diagram shows that loss of cell junctions are critical to metastasis and formation of malignant tumors.  The diagram below shows the same trend, and further shows that chances of successful recovery from cancer decrease as cancer cells lose their adherens junctions and desmosomes.

chances of successful clinical resolution decrease as cell junctions are lost

 

As a result of this work, numerous new cancer drugs are aimed at making sure cancer cells maintain their connections to surrounding cells.