Characteristics, Vs Normal cells, Types and Microscopy
Overview: Cancer and Cancer Cells
Essentially, cancer is a disease of mitosis. As such, it occurs when normal cells are transformed into cancerous cells and proliferate uncontrollably. Cancer cells, therefore, are normal cells whose genes (several genes) have been damaged/mutated which in turn cause the cell as a whole to respond differently to signals that control the lifespan of a normal cell.
Because they do not respond to signals/instructions that control the development and death of normal cells, cancer cells continue to grow and proliferate and even invade other parts of the body. In the process, some of the cancer cells end up forming tumors not only at the first region to be affected (lungs etc) but also result in secondary malignant growths away from the primary site (metastasis).
Some of the main characteristics of cancer cells that differentiate them from other normal cells include:
- Abnormally shaped and significantly vary in size
- Incapable of self-repair
- Do not go through normal apoptosis
- Do not perform normal cell functions (as is the case with specialized cells)
Causes of Cancer Cells
Before looking at some of the main characteristics of cancer cells in detail, it is worth understanding what causes cancer.
Basically, the transformation of a cell from normal to cancerous is caused by agents that are collectively known as carcinogens. On the other hand, such biological factors as viruses (e.g. HPV) have been shown to increase the risk of cancer in various parts of the body.
Here, these initiating agents, which include carcinogens (e.g. radiations, UV light, food additives, various chemicals, and cigarette smoke, etc) and viruses transform normal cells by causing damage to DNA and thereby inducing mutations.
Normal cells, however, do not generally transform into cancer cells within a few days. This may happen gradually with exposure to the initiating agent. For instance, this may occur as a result of smoking cigarettes for several years. As the cells become exposed to this initiating agent, several genes may end up being damaged which in turn may not only affect cell functions, but also the cell cycle.
Depending on the impact of the carcinogen on the cell, the type of cancer that develops (from the cancerous cells) would be different from other types of cancer. For instance, while some of the tumors that develop may be benign; others may be more aggressive and rapidly spread to other parts of the body.
* While there are different types of cancer cells as there are cancers, they all share a number of characteristics.
Characteristics of Cancer Cells
Compared to Normal Cells
For the most part, normal cells adopt a specific, uniform cell shape once they differentiate. Depending on the cell, this may allow the cell to effectively perform their function in the body.
A good example of this is red blood cells that have a biconcave shape that allows them to carry red blood cells effectively. Cancer cells, on the other hand, are irregular in shape and misshapen with varying sizes. Given that they do not attach to each other as other normal cells do (in various tissues) they also appear as a chaotic collection of cells when viewed under the microscope.
The irregular shape of cancer cells has also been identified in the nucleus and nucleolus of cancer cells. Whereas normal cells have a nucleus with a smooth appearance that is spherical in shape, the nucleus of cancer cells tends to be irregular with bulges (blebs). This irregularity is also evident on the nucleolus and may be divided into multiple nucleoli.
Normal cells in the body live within a certain period of time and then die. For instance, red blood cells have a lifespan of about 120 days after which they undergo senescence.
Through this process, aged red cells are cleared while new ones continue to be produced to transport oxygen around the body. Cells in the body (normal cells) are destroyed through a process known as apoptosis in the event that damage to parts of the cell (DNA, etc) cannot be repaired.
For cancer cells, such mechanisms as cell repair are defective which allows the cells to continue living through an indefinite number of population doubling. Moreover, cancer cells do not respond to signals that initiate apoptosis as is the case with normal cells, which allows them to continue proliferating both in vivo and in vitro.
For normal cells, each division is accompanied by the shortening of the telomeres (at the ends of the chromosomes). When these regions wear out, the cell eventually dies. For cancer cells, however, the length of this part of the cell is retained which allows the cells to continue dividing.
A good example of this is the HeLa cell line belonging to a woman by the name Henrietta Lacks who died in 1951 of cervical cancer.
In order to produce the energy required to effectively perform their functions, normal cells need oxygen and sugar (glucose) among other requirements.
Transformed cells, however, have been shown to have lower growth requirements compared to normal cells. For instance, in a study where 3T3 fibroblasts were transformed using several viruses, their growth in culture was shown to be successful despite the lack of various serum growth factors.
Unlike normal cells, cancer cells have also been shown to be capable of producing their own growth factors that can also stimulate the proliferation of other cells in their surroundings.
In both glycolysis and the tricarboxylic acid cycle, studies have shown cancerous cells to poorly use oxygen for energy production. Instead, they have been shown to use more glucose (to as much as 10 times more than normal cells) for energy production. Here, the sugar is converted to lactic acid before being recycled in the liver.
In some cases, these cells have also been shown to behave like metabolic parasites in that they drain energy from the surrounding cells. This provides them with the energy required for proliferation. At the same time, it also causes the organism to experience fatigue.
Cancer Cells induce Angiogenesis
One of the other characteristics of cancerous cells is their vascularizing abilities. By producing angiogenic factors (TAF), cancer cells stimulate endothelium growth and thus stimulate the formation of new blood vessels.
This allows the cells to receive more nutrients (high amounts of glucose) required for proliferation and growth. While angiogenesis plays an important role in supplying cancer cells, it has also been shown to highly contribute to metastasis.
Based on a variety of studies, the density of microvessels has been shown to be higher in malignant cancers as compared to benign neoplasias. Using the new vessels, cancer cells are able to migrate to other parts of the body and cause the spread of cancer to these regions.
Adhesion (cell to cell adhesion and cell to extracellular matrix adhesion)
For normal cells, cell to cell adhesion and cell to extracellular matrix adhesion has been shown to play an important role in enhancing cell growth, differentiation, multiplication and function. Disruption of the same has been associated with motility of the cells as well as invasion through the extracellular matrix.
Compared to normal cells, cancer cells have been shown to be less adhesive due to loss of such surface adhesive molecules as E-cadherin. Reduced adhesive properties of these cells have been associated with alterations observed in their general morphology. Despite reduced adhesiveness, increased motility does not occur.
Because of the fact that cancer cells are less adhesive compared to normal cells, they can easily invade the extracellular matrix and even migrate through the vascular system to other parts of the body. In malignant cancer, this allows the cells to spread easily to other parts of the body causing the disease to continue spreading.
Some of the other characteristics of cancer cells include:
- Altered cellular differentiation
- They can evade the immune system that would otherwise destroy them
- The protein that checks for gene damage (p53) in normal cells (thus initiating repair or cell damage) is defective in cancer cells which prevents their death
- DNA hypomethylation in cancer cells promotes carcinogenesis
Types of Cancer Cells
Today, well over 100 types of cancer have been identified. Because they arise from different types of cells in the body, the names given to the different types of cancer are derived from the affected cells.
The different types of cancer cells can be identified by looking at the different types of cancers that have been identified.
While there are many types of cancers that have been identified, some of the most common include:
· Sarcoma - is the type of cancer that affects bones and the soft tissues. As such, it is likely to affect the blood vessels, tendons, and ligaments as well as muscles. An example of sarcoma is Osteosarcoma which is one of the most common bone cancers.
· Leukemia - is a type of cancer that begins at blood-forming tissue. Given that it affects the tissue that produce white cells, alterations result in increased production of abnormal white cells that accumulate at the bone marrow and ultimately outnumber normal cells. This not only affects the normal ration of blood cells in the body, but also their ability to effectively carry out their functions.
· Lymphoma - is the type of cancer that arises from altered lymphocytes. As such, it results in the production of abnormal lymphocytes that spread through such vessels as the lymph vessels to other organs.
· Melanoma - Melanoma starts from cells known as melanocytes. These are the cells responsible for the production of melanin. As a result, the effects of the disease can be observed on the skin and eyes.
Some of the other types of cancer, and thus cancer cells include:
· Brain and spinal cord cancer - There are different types of brain and spinal cord cancer that are named based on the origin of the disease (e.g. astrocytes give rise to astrocytic tumors).
· Myeloma- Cancer that begins in the plasma cells (myeloma cells).
· Germ cell tumors - Starts at the germ cells.
· Carcinoma - There are different types of carcinoma depending on origin. Among others, they include Adenocarcinoma, Anaplastic carcinoma and Squamous cell carcinoma
* Cancer cells may also be classified on the basis of the tumor they form. While some cells form lumps/growths that spread out and invade other parts of the body (malignant tumors), some remain intact and do not spread out (benign tumors).
* Although all tumors are reason for concern, benign tumors are easy to manage and can be removed through surgery compared to malignant ones that tend to spread to other parts of the body through the lymphatic and blood vessels.
Microscopy (Squamous Cell Carcinoma)
Apart from electron microscope techniques, different types of light microscope techniques have been used to observe cancer cells.
Using peripheral blood films has proved effective in observing cancer cells of the blood (lymphoma) while Giemsa staining has been used to observe squamous cell (cases of carcinoma) under the light microscope.
This section gives focus to the use of a confocal microscope to observe carcinoma cancer cells (squamous-cell carcinoma).
- A confocal microscope
- Acridine orange (AO) stain
- Clean glass slide
- Flat wooden sticks/ cotton swabs
- 100% alcohol
- 1% acetic acid
- Distilled water
- Phosphate buffer solution
- Sample (squamous cell carcinoma from the buccal mucosa)
- Using a flat wooden stick or cotton swab, smear the sample onto a clean glass slide
- Fix the sample using 100 percent alcohol (for about 15 minutes)
- Rinse the slide in 1 percent acetic acid for a few seconds
- Wash the sample using distilled water for about 1 minute (two changes)
- Stain the sample using 0.01 percent acridine orange for about 3 minutes
- Using phosphate buffer solution, de-stain the slide for about 1 minute -differentiate in 0.1 M CaCl for about a minute
- Use phosphate buffer solution to remove excess CaCl
- Add a drop of the phosphate buffer solution to mount and observe under the microscope
See more on cell staining.
When viewed under the microscope, significant nuclear change is evident. Here, nuclei (green in color) are seen as scattered particles. The cytoplasm, on the other hand, takes up a dull olive green coloration.
* The use of Papanicolaou stain also makes the nuclei more visible under the microscope (pink/purple in color) where the cytoplasm appears more translucent.
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Halliday Idikio. (2011). Human Cancer Classification: A Systems Biology- Based Model Integrating Morphology, Cancer Stem Cells, Proteomics, and Genomics.
Raymond W. Ruddon. (2003). What Makes a Cancer Cell a Cancer Cell? Holland-Frei Cancer Medicine. 6th edition.
Shalmica Jackson, Daniela Grabis, and Caroline Manav (2018). Giemsa: The Universal Diagnostic Stain.
Shyam Prasad Reddy, Pratibha Ramani, and Purshotam Nainani. (2013). Confocal microscopy and exfoliative cytology. NCBI.