The Difference Between Normal and Malignant Cells

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Malignant cells are abnormal cells associated with cancer. They are sometimes referred to as neoplastic cells and they may be found as part of a tumor such as a melanoma, or diffusely spread as displayed in leukemia. So what is the difference between normal and malignant cells? There are three main features of malignant cells which enable them to be identified. These are anaplasia (the failure to differentiate), invasiveness (the ability to grow out of control) and metastasis (the ability to spread and divide elsewhere in the body).

Anaplasia - Malignant Cells Lose the Ability to Differentiate

Normal cells are adapted to perform a particular role within the body; and their morphology and expression of genes will reflect that function. During cell development, normal cells differentiate to enable them to perform their function efficiently. Neoplastic cells lose the ability to differentiate, so under the microscope they will appear abnormal compared with the healthy cells around them.

Typical histological features of malignant cells indicative of anaplasia include an unusually high nuclear to cytoplasmic ratio, and variation in size and shape of both the cells themselves (cellular pleomorphism) and the nuclei (nuclear pleomorphism).[1]

Invasiveness - Malignant Cells Divide at an Increased Rate

Malignant cells lack certain growth-controlling enzymes and this allows them to divide and grow rapidly, outside the control of the body’s normal growth regulation systems. Malignant cells are resistant to apoptosis, which is the normal cell’s mechanism of programmed cell death triggered by DNA damage. They are also capable of dividing without the intervention of external growth factors, and they do not respond to the body’s normal signals to inhibit growth.

The abnormal growth of malignant cells is due to mutations in key genes: an example is p53, which is a tumor suppressor gene involved in many cell processes including programmed cell death, cell cycle control and DNA repair. P53 tumor suppressor gene mutations are found in more than half of all cancer cases.[2]

Under the microscope, the nuclei of malignant cells often stain darker than normal nuclei, and a large proportion of cells may be observed undergoing mitosis (cell division), some abnormally.[3]

Not only can malignant cells divide and grow faster than normal cells; they also have the ability to secrete enzymes capable of digesting extracellular matrix material (connective tissue). An important enzyme secreted by malignant cells is major excreted protein (MEP) which has been shown to digest fibrinonectin, collagen and laminin.[4] The destruction of connective tissue in this way by malignant cells allows them to invade healthy tissue more easily.

A rapidly growing collection of malignant cells needs constant nourishment, and neoplastic cells are often capable of angiogenesis (the stimulation of blood vessel growth). Malignant cells are known to express a unique protein known as tumor angiogenesis factor (TAF) which can diffuse at least 5mm through tissue and stimulates the growth of new capillaries to supply the developing tumor with nutrients.[5]

Metastasis - Formation of New Tumors in Other Parts of the Body

Malignant cells are capable of breaking away from the tumor and moving to other parts of the body, where they divide to form new tumors. There are three methods by which malignant cells may spread. Local invasion occurs through invasive growth to nearby areas. This often takes place along the lines of least resistance, for example along nerve bundles. Malignant cells frequently metastasise through lymphatic spread, where the tumor cells travel via the lymphatic drainage system to local lymph nodes. In vascular spread, the malignant cells are carried through the veins to other parts of the body: common examples include metastatic tumors in the lung, and gut tumors spreading to infect the liver.[6]

Immunological Differences

In addition to the differences in morphology and growth which distinguish malignant cells from normal cells, it has long been known that malignant cells express different antigens from normal cells. [7] This immunological difference between normal and malignant cells may provide opportunities to develop new treatments and preventative interventions for cancer in the future.


[1] [3] [6] HG Burkitt, A Stevens, JS Lowe, B Young “Wheater’s Basic Histopathology” Churchill Livingstone ISBN 0-443-05088-0

[2] C Harris “p53 Tumor Suppressor Gene: At the Crossroads of Molecular Carcinogenesis, Molecular Epidemiology, and Cancer Risk AssessmentEnvironmental Health Perspectives 104: Suppl 3 (1996)

[4] S Gal, MM Gottesman “The Major Excreted Protein of Transformed Fibroblasts Is an Active Acid-ProteaseThe Journal of Biological Chemistry 261:1760-1965 (1986)

[5] J Folkman “Tumor Angiogenesis FactorCancer Research 34:2109-2113 (1974)

[7] SD Smith, M Shatsky, PS Cohen “Monoclonal Antibody and Enzymatic Profiles of Human Malignant T-Lymphoid Cells and Derived Cell LinesCancer Research 44:5657-5660 (1984)