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The number of cells in a tissue is determined by the balance between cell division and cell death. Uncontrollable cell division leads to formation of abnormal growths called tumors. Tumors can be benign or malignant. Benign tumors are slow-growing and constrained by surrounding connective tissue so they do not spread to other organs. They can still be harmful or even kill by pressing on nearby nerves, brain tissue or blood vessels. Examples of benign tumor include pituitary tumors which may press on optic nerves and cause loss of vision. Cancers are malignant tumors – tumors that can spread beyond of the limit of original organ where it comes from and to other organs of the body.
How cancer starts
Cancer starts from a damage in the DNA of a cell. This DNA damage is called mutation. Mutations happen when the cell duplicates its DNA prior to cell division and makes mistakes. These damages are usually detected and repaired before the cell can divide but sometimes, some of them may be ignored and transferred to daughter cells.
If the mutation is located in one of many genes that control the cell cycle, it may affect the regulation of cell cycle in the cell carrying it, and make the cell divide faster than it supposed to. Usually, one mutation is not enough to cause cancer, but as it makes the cell cycle control less reliable, many more DNA damages/mutations would go unnoticed. Cancer is usually the result of accumulation of many mutations of genes involved in cell cycle control and DNA repair. This commonly happens over a long period of time, over many rounds of cell divisions, and this explains why cancers are more common in older people.
Fig. 1 Cancer cells reproduce to from tumor. Click on image to see a larger version on Alila Medical Media website where the image is also available for licensing.
Some people are said to be predisposed to cancer. This is because they are born with a mutation that makes them more likely to develop a certain type of cancer. This mutation alone is not enough to cause cancer but it starts the process of making cells cancerous. The person carrying it is one step further down the road towards developing a cancer than others who do not have the mutation.
Genes that are mutated in cancer
Three main classes of genes that are found mutated in cancers:
Proto-oncogenes – when mutated become oncogenes. Most cells do not divide until a growth factor binds to a receptor on its surface and instruct it to do so. Growth factor binding activates a cascade of events preparing the cell for division. Proto-oncogenes encode for normal growth factors and growth factor receptors. Oncogenes encode for abnormal versions of these. These malfunctional growth factors and receptors instruct the cells to divide non-stop causing cancer. A well known example of oncogene is ras, which encodes for a mutated growth factor receptor.
Tumor suppressors (TS) genes – these encode for cell cycle inhibitors, a class of molecules that prevent the progression of the cell cycle. Many of these arrest the cell cycle in G1 phase by binding to and inactivating cyclin-CDK complexes. A famous TS gene is p53, which is found mutated in majority of cancers including colon, brain, breast, lung cancers and leukemia.
DNA repair genes – these encode for enzymes that repair damage in DNA before the cell can divide. Mutations in these genes lead to accumulation of mutations that eventually make the cell cancerous.
How cancer spreads
Cancer cells do not stick together like normal cells, they move and invade nearby tissues, organs, this is local spread. They may also spread to further away organs by means of blood and lymph circulation, this is systemic spread. Metastasis is the spreading of cancers to non-adjacent organs. Cancer cells from the original tumor (primary cancer) can break out and maybe taken up by a blood or a lymph vessel for a ride throughout the body. They can then squeeze out from the vessels into other tissues and start a new tumor growth in the new location which will become secondary cancer.
Fig. 2 : Cancer cells squeeze through the wall of blood and lymph capillary. Click on image to see a larger version on Alila Medical Media website where the image is also available for licensing.
Where do cancers usually spread and why?
While travelling in the bloodstream, cancer cell usually stops at the first place where the vessel getting so narrow that it gets stuck. As blood flow from most organs goes to the capillaries of the lungs, this is where cancers spread the most. Lungs are indeed the most common site of secondary cancers.
Fig. 3 : Primary cancer from the pancreas metastases to the lungs through the bloodstream. Click on image to see a larger version on Alila Medical Media website where the image is also available for licensing.
Likewise, while travelling in the lymphatic system, cancer cells commonly get stuck in nearest lymph nodes, where the vessels get narrower. This is the reason why surgeons usually remove nearby lymph nodes when removing tumors.
