There are many differences between cancer cells and normal cells. Some of the differences are well known, whereas others have only been recently discovered and are less well understood. You may be interested in how cancer cells are different as you are coping with your own cancer or that of a loved one. For researchers, understanding how cancer cells function differently from normal cells lays the foundation for developing treatments designed to rid the body of cancer cells without damaging normal cells.
The first portion of this list discusses the basic differences between cancer cells and healthy cells. For those who are interested in some of the more difficult-to-understand differences, the second portion of this list is more technical.
A brief explanation of the proteins in the body that regulate cell growth is also helpful in understanding cancer cells. Our DNA carries genes that in turn are the blueprint for proteins produced in the body. Some of these proteins are growth factors, chemicals that tell cells to divide and grow. Other proteins work to suppress growth. Mutations in particular genes (for example, those caused by tobacco smoke, radiation, ultraviolet radiation, and other carcinogens) can result in the abnormal production of proteins. Too many may be produced, or not enough, or it could be that the proteins are abnormal and function differently.
Cancer is a complex disease, and it is usually a combination of these abnormalities that lead to a cancerous cell, rather than a single mutation or protein abnormality.
Below are some of the major differences between normal cells and cancer cells, which in turn account for how malignant tumors grow and respond differently to their surroundings than benign tumors.
Growth – Normal cells stop growing (reproducing) when enough cells are present. For example, if cells are being produced to repair a cut in the skin, new cells are no longer produced when there are enough cells present to fill the hole; when the repair work is done. In contrast, cancer cells don’t stop growing when there are enough cells present. This continued growth often results in a tumor (a cluster of cancer cells) being formed. Each gene in the body carries a blueprint that codes for a different protein. Some of these proteins are growth factors, chemicals that tell cells to grow and divide. If the gene that codes for one of these proteins is stuck in the “on” position by a mutation (an oncogene)—the growth factor proteins continue to be produced. In response, the cells continue to grow.
Communication – Cancer cells don’t interact with other cells as normal cells do. Normal cells respond to signals sent from other nearby cells that say, essentially, “you’ve reached your boundary.” When normal cells “hear” these signals they stop growing. Cancer cells do not respond to these signals.
Cell repair and cell death – Normal cells are either repaired or die (undergo apoptosis) when they are damaged or get old. Cancer cells are either not repaired or do not undergo apoptosis. For example, one protein called p53 has the job of checking to see if a cell is too damaged to repair and if so, advise the cell to kill itself. If this protein p53 is abnormal or inactive (for example, from a mutation in the p53 gene,) then old or damaged cells are allowed to reproduce. The p53 gene is one type of tumor suppressor gene that code for proteins that suppress the growth of cells.
Stickiness – Normal cells secrete substances that make them stick together in a group. Cancer cells fail to make these substances, and can “float away” to locations nearby, or through the bloodstream or system of lymph channels to distant regions in the body.
Ability to Metastasize (Spread) – Normal cells stay in the area of the body where they belong. For example, lung cells remain in the lungs. Cancer cells, because they lack the adhesion molecules that cause stickiness, are able to travel via the bloodstream and lymphatic system to other regions of the body—they have the ability to metastasize. Once they arrive in a new region (such as lymph nodes, the lungs, the liver, or the bones) they begin to grow, often forming tumors far removed from the original tumor. (Learn more about how cancer spreads.)
Appearance – Under a microscope, normal cells and cancer cells may look quite different. In contrast to normal cells, cancer cells often exhibit much more variability in cell size—some are larger than normal and some are smaller than normal. In addition, cancer cells often have an abnormal shape, both of the cell, and of the nucleus (the “brain” of the cell.) The nucleus appears both larger and darker than normal cells. The reason for the darkness is that the nucleus of cancer cells contains excess DNA. Up close, cancer cells often have an abnormal number of chromosomes that are arranged in a disorganized fashion.
The rate of growth – Normal cells reproduce themselves and then stop when enough cells are present. Cancer cells reproduce rapidly before the cells have had a chance to mature.
Maturation – Normal cells mature. Cancer cells, because they grow rapidly and divide before cells are fully mature, remain immature. Doctors use the term undifferentiated to describe immature cells (in contrast to differentiated to describe more mature cells.) Another way to explain this is to view cancer cells as cells that don’t “grow up” and specialize into adult cells. The degree of maturation of cells corresponds to the 'grade' of cancer. Cancers are graded on a scale from 1 to 3 with 3 being the most aggressive.
Evading the immune system – When normal cells become damaged, the immune system (via cells called lymphocytes) identifies and removes them. Cancer cells are able to evade (trick) the immune system long enough to grow into a tumor by either by escaping detection or by secreting chemicals that inactivate immune cells that come to the scene. Some of the newer immunotherapy medicationsaddress this aspect of cancer cells.
Functioning – Normal cells perform the function they are meant to perform, whereas cancer cells may not be functional. For example, normal white blood cells help fight off infections. In leukemia, the number of white blood cells may be very high, but since the cancerous white blood cells are not functioning as they should, people can be more at risk for infection even with an elevated white blood cell count. The same can be true of substances produced. For example, normal thyroid cells produce thyroid hormone. Cancerous thyroid cells (thyroid cancer) may not produce thyroid hormone. In this case, the body may lack enough thyroid hormone (hypothyroidism) despite an increased amount of thyroid tissue.
Blood supply – Angiogenesis is the process by which cells attract blood vessels to grow and feed the tissue. Normal cells undergo a process called angiogenesis only as part of normal growth and development and when new tissue is needed to repair damaged tissue. Cancer cells undergo angiogenesis even when growth is not necessary. One type of cancer treatment involves the use of angiogenesis inhibitors—medications that block angiogenesis in the body in an effort to keep tumors from growing.
This list contains further differences between healthy cells and cancer cells. For those who wish to skip these technical points, please skip to the next subheading labeled summarizing the differences.
Evading growth suppressors – Normal cells are controlled by growth (tumor) suppressors. There are three main types of tumor suppressor genes that code for proteins that suppress growth. One type tells cells to slow down and stop dividing. One type is responsible for fixing changes in damaged cells. The third type is in charge of the apoptosis noted above. Mutations that result in any of these tumor suppressor genes being inactivated allow cancer cells to grow unchecked.
Invasiveness – Normal cells listen to signals from neighboring cells and stop growing when they encroach on nearby tissues (something called contact inhibition.) Cancer cells ignore these cells and invade nearby tissues. Benign (non-cancerous) tumors have a fibrous capsule. They may push up against nearby tissues but they do not invade/intermingle with other tissues. Cancer cells, in contrast, don’t respect boundaries and invade tissues. This results in the fingerlike projections that are often noted on radiologic scans of cancerous tumors. The word cancer, in fact, comes from the latin word for crab used to describe the crablike invasion of cancers into nearby tissues.
Energy Source – Normal cells get most of their energy (in the form of a molecule called ATP) through a process called the Krebs cycle, and only a small amount of their energy through a different process called glycolysis. Whereas normal cells produce most of their energy in the presence of oxygen, cancer cells produce most of their energy in the absence of oxygen. This is the reasoning behind hyperbaric oxygen treatments that have been used experimentally (with disappointing results thus far) in some people with cancer.
Mortality/Immortality – Normal cells are mortal, that is, they have a lifespan. Cells aren’t designed to live forever, and just like the humans they are present in, cells grow old. Researchers are beginning to look at something called telomeres, structures that hold DNA together at the end of the chromosomes, for their role in cancer. One of the limitations to growth in normal cells is the length of the telomeres. Every time a cell divides, the telomeres get shorter. When the telomeres become too short, a cell can no longer divide and the cell dies. Cancer cells have figured out a way to renew telomeres so that they can continue to divide. An enzyme called telomerase works to lengthen the telomeres so that the cell can divide indefinitely—essentially becoming immortal.
Ability to 'hide' - Many people wonder why cancer can recur years, and sometimes decades after it appears to be gone (especially with tumors such as estrogen receptor positive breast cancers.) There are several theories why cancers may recur. In general, it's thought that there is a hierarchy of cancer cells, with some cells (cancer stem cells) having the ability to resist treatment and lie dormant. This is an active area of research, and extremely important.
Genomic instability – Normal cells have normal DNA and a normal number of chromosomes. Cancer cells often have an abnormal number of chromosomes and the DNA becomes increasingly abnormal as it develops a multitude of mutations. Some of these are driver mutations, meaning they drive the transformation of the cell to be cancerous. Many of the mutations are passenger mutations, meaning they don’t have a direct function for the cancer cell. For some cancers, determining which driver mutations are present (molecular profiling or gene testing) allows physicians to use targeted medications which specifically target the growth of the cancer. The development of targeted therapies such as EGFR inhibitors for cancers with EGFR mutations is one of the more rapidly growing and progressing areas of cancer treatment.
As noted above, there are many differences between normal cells and cancer cells. Also noteworthy is the number of “checkpoints” that need to be bypassed for a cell to become cancerous.
The cell needs to have growth factors that prompt it to grow even when growth is not necessary.
The has to evade proteins that direct cells to stop growing and die when they become abnormal.
The cell needs to evade signals from other cells,
The cells need to lose the normal “stickiness” (adhesion molecules) that normal cells produce.
All in all, it is very difficult for a normal cell to become cancerous, which may seem surprising considering that one in two men and one in three women will develop cancer in their lifetime. The explanation is that in the normal body, roughly three billion cells divide every single day. “Accidents” in the reproduction of the cells caused by heredity or carcinogens in the environment during any of those divisions can create a cell that, following further mutations, can develop into a cancer cell.
As noted above, there are many differences in cancer cells and normal cells which make up either benign or malignant tumors. In addition, there are ways that tumors containing cancer cells or normal cells behave in the body. Some of these additional differences are noted in this article on the differences between benign and malignant tumors.
After discussing these many differences between cancer cells and normal cells, you may be wondering if there are differences between cancer cells themselves. That there may be a hierarchy of cancer cells—some having different functions than others—is the basis of discussions looking at cancer stem cells as discussed above.
We still don't understand how cancer cells can seemingly hide for years or decades and then reappear. It's thought by some that the 'generals' in the hierarchy of cancer cells referred to as cancer stem cells may be more resistant to treatments and have the ability to lie dormant when other soldier cancer cells are eliminated by treatments such as chemotherapy. While we currently treat all the cancer cells in a tumor as being identical, it's likely that in the future treatments will take into further consideration some of the differences in cancer cells in an individual tumor.
Sources:
DeBaradinis, R. et al. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metabolism. 2008. 7(1):11-20.
National Cancer Institute. SEER Training Module. Cell Biology of Cancer. https://training.seer.cancer.gov/disease/cancer/biology/
National Cancer Institute. What is Cancer? Updated 02/09/15. https://www.cancer.gov/about-cancer/understanding/what-is-cancer
Nio, K., Yamashita, T., and S. Kaneko. The Evolving Concept of Liver Cancer Stem Cells. Molecular Cancer. 2017. 16(1):4.
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