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Cancer Cells: Useful Notes on Cancer Cells!
Cancer cells are characterized by an uncontrolled cell growth, invasion of other tissues, and dissemination to other sites of the organism producing secondary tumors.
All these characteristics suggest that cancer cells have escaped from the controls that regulate normal growth.
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Cancerous tumors are monoclonal, i.e., derive from the division of a single cell, which has been transformed into a cancer cell.
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Cancer cells are structurally and biochemically different from normal cells. For example, the karyotype is frequently abnormal, with changes in chromosome number or with chromosomal alterations. Malignant cells generally have a higher glycolytic activity. The cytoskeleton, which is composed of a network of microtubules, actin microfilaments and intermediate filaments, is reduced or disorganized.
Surface changes in cancer cells:
Cancer Cells undergo many changes in the plasma membrane, especially in the cell coat. Cell coat contains abundant amount of glycosaminoglycons which is responsible for more negative charges on the cell coat. Many cancer cells show electrical uncoupling owing to the disappearance of gap junctions.
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In cancer cells glycoprotein receptors tend to diffuse more easily within the lipid bilayer than they do in normal cells. This great diffusibility of receptors (also found in normal cells during mitosis) may be caused by disorganization of the microfilaments that normally are attached to the plasma membrane and that reduce the mobility of receptors.
Differences also exist in the glycolipid and glycoprotein content, in a reduction in the amount of gangliosides and in their enzymes of synthesis. In cancer cells, certain proteins of the membrane disappear and sugar uptake increases. Cancer cells frequently release intracellular enzymes to the medium.
A major protease secreted by cancer cells acts on plasminogen and converts it into plasmin. Plasmin is a proteolytic enzyme that dissolves blood clots and also removes exposed protein groups at the cell surface. If plasminogen is removed from the medium, the morphology of cancer cells return to normal.
Frequently, cancer cells carry new antigens not present in normal cells, which can induce immunological response that in certain favourable conditions may eliminate cancer cells. The production of specific antibodies against such antigens could be a way of controlling some tumors.
Cancer cells and iron transport:
One important difference between normal cells and cancer cells is their method of metabolizing iron and trace metal ions. They transport and deliver iron to the cells through transferrin, a glycoprotein present in blood plasma. It binds the metal and associates it with specific transferrin receptors on the cell membrane.
After its penetration inside the cell, the iron binds to other proteins, such as ferritin, and is deposited for use in many enzymatic systems (e.g., cytochromes). Transferrin is essential to the growth of normal cells in cultures and should be present in the medium to maintain the cell cycle. Normal cells probably adapt to iron deprivation by changing the transferrin binding capacity.
Cancer cells that transformed by an oncogenic virus secrete a low molecular weight agent siderophore-like growth factor, which has a high capacity for binding iron (acts as a chelating agent) and transporting it inside the cell (acts as an ionophore or channel).
Fibronectin and cancer cell:
One of the major chemical components of the cell coat is fibronectin, a high molecular weight glycoprotein. Together with other glycoproteins, fibronectin is found in the “footprints” that a moving cultured cell leaves on the substratum.
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Fibronectin originally called LETS (large external transformation sensitive) protein, is absent or drastically reduced in cultured cells undergoing cancerous transformation. This change may explain the tendency of cancer cells to break up connections with other cells, to invade tissues locally, and to metastasize (i.e., to invade distant tissues through lymph and blood vessels).
Addition of fibronectin to cultured transformed cells produces changes in their behaviour, causing them to acquire a more normal appearance. For example, they attach more readily to the substrate, becomes more flattened and align with one another in a monolayer. Their cytoskeleton also becomes more organized under the influence of fibronectin.
Loss of control of growth in cancer cells:
Cancer cells are unable to adhere with neighbouring cells and do not show contact inhibition of normal cell type. Such cells have more blebs on the cell surface than normal cells. Cancer cells continue to multiply and pile up forming irregular masses several layers deep.
Normal cells undergo a limited number of divisions (between 50 and 100 for human fibronlasts) in cultures that are repeatedly sub cultured. Thereafter cell ages and dies. Malignant cells are potentially immortal and continue to divide indefinitely.
Transformed cells have no inhibition control because they are not dependent on external growth factors, which control the growth of normal cells. The uncontrolled growth is the main characteristic of a cancer cell.
Virus as oncogenic agents:
The carcinogenic agents (chemical, physical and biological) affect the DNA by changing the nucleotide sequence and by causing mutation.
Carcinogenic agents are ionizing radiations, many alkylating drugs and polycyclic aromatic hydrocarbons.
Biological oncogenic mechanism (i.e., produced by certain viruses):
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Certain viruses can transform the normal cells in culture into cancerous cells. Oncogenic agents are different viruses. These contain either DNA or RNA. In both cases, the virus is able to infect and to transform the cell.
The viral genome becomes integrated and hidden in the cell host DNA and both of them replicate at each cell division. In addition, viral genome is able to produce RNA (transcription) and special proteins (translation), which can be detected in the transformed cell.
Among the DNA viruses are polysoma and simian virus 40 (Sv40). These are very small of icosahedral shape (20 sufaces) and about 45 nm in diameter. The DNA molecule is circular and double-stranded.
The viral genome of Sv40 has a few genes that code for the viral capsid and produce a protein called T (tumor) antigen, which accumulates in the cell nucleus. This protein T appears to be responsible for the transformation. In a transformed cell only the genes producing the T antigen are expressed and the viral capsid is not produced.
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Other oncogenic viruses are adenovirus and the Epstein-Barr virus. They produce mononucleosis and supposed to produce human cancer called Burkitt lymphoma, which is endemic in Africa.
Viruses that contain RNA belong to the retroviruses, which have a single RNA chain. These viruses have an inner core of RNA with a few proteins. This inner core is surrounded by a shell and by an outer envelope, which are provided by the plasma membrane of the host cell. RNA viruses are natural agents in animal tumors, especially in rodents.
This virus can infect the egg and thus pass from one generation to another. They may also pass to the offspring through mother’s milk. The single RNA genome of the virus serves as a template for the production of a complementary DNA molecule by reverse transcriptase. Then a double-stranded DNA of the viral genome is produced, which becomes integrated in the host DNA.
