CANCER CELLS

Diseases in which tissues grow and spread unrestrained throughout the body, eventually choking off life describe the term "cancer". Cancers can originate in almost any organ. Depending on the cell type involved, they are grouped into several different categories: Carcinoma, which account for about 90% of all cancers, arise from the epithelial cells, for example, lung, breasts and colon cancer. Sarcomas, develop from supporting tissues such as bone, cartilage, fat and muscle. Lymphomas (tumors that grow as solid masses of tissue) and Leukemias (cancer cells proliferate mainly in the blood) arise from cells of blood and lymphatic origin.
The danger posed by the disease comes from a combination of two properties: 
the ability of cells to proliferate in an uncontrolled way and
 their ability to spread through the body.

Tumor arises when the balance between cell division and cell differentiation or death is disrupted.

A cancer is an abnormal type of tissue growth in which some cells divide and accumulate in an uncontrolled, relatively autonomous way, leading to a progressive increase in the number of dividing cells. The resulting mass of growing tissue is called a tumor (or neoplasm). 

Cell differentiation is the process by which cells acquire the specialized properties that distinguish different types of cells from each other. As cells acquire these specialized traits, they generally lose the capacity to divide. Cell division is carefully balanced with cell differentiation and death so that no net accumulation of dividing cells takes place. 

For example in the skin the new cells are generated by the basal layer giving rise to two cells with different fates. One cell stays in the basal layer and retains the capacity to divide, whereas other cell loses the capacity to divide and moves toward the outer skin surface. Eventually it dies and is shed from the outer skin. This arrangement ensures that there is no increase in the number of dividing cells. 

In tumors, this finely balanced arrangements is disrupted and cell division is uncoupled from cell differentiation and death.  This give rise to two cells that both continue to divide, thereby feeding a progressive increase in the number of dividing cells. As the dividing cells accumulate, the normal organization and function of the tissue gradually become disrupted, giving rise to tumor.

Based on the differences in their growth patterns, tumors are classified as either benign tumor or malignant. Benign tumors grow in a confined local area and are rarely dangerous. In contrast, malignant tumors are capable of invading surrounding tissues, entering the bloodstream, and spreading to distant parts of the body. 

The term 'cancer' refers to any malignant tumor- that is, any tumor that can spread from its original location to other sites.

 Cancer cell proliferation is anchorage independent and insensitive to population density

Normal cells don't grow well in culture if they are suspended in a liquid medium or in a semisolid material such as soft agar. But when provided with a solid agar they can attach to, normal cells become anchored to the surface, spread out, and begin to proliferate. In contrast, cancer cells grow well not only when they are anchored to a solid surface but also when they are freely suspended in a liquid or semisolid medium. Cancer cells are therefore said to exhibit anchorage-independent growth.

Normal cells get self- destructed by apoptosis in the absence of cell surface proteins called integrins. Triggering apoptosis in the absence of proper anchorage is one of the safeguards that prevents normal cells from floating away and setting up housekeeping in another tissue. Because cancer cells are anchorage independent, they circumvent this safeguard.

Cancer cells also differ from normal cells in their response to crowded conditions in culture. Once the monolayer stage is reached, cell division stops in case of normal cells. This phenomenon is referred as density dependent inhibition of growth. Cancer cells exhibit reduced sensitivity to this phenomena and thus do not stop dividing even when the monolayer stage is reached. instead, cancer cells continue to divide and gradually begin piling up on one another.

Cancer cells are immortalized by mechanisms that maintain telomere length.

When most normal cells are grown in culture, they divide a limited number of times. But cancer cells exhibit no such limit and continue dividing indefinitely, behaving as if they were immortal. This is because, when normal cells divide, the telomeric DNA sequences are lost from the ends of each chromosome every time DNA replicates. Most cancer cells accomplish this feat by producing telomerase, the enzyme that adds telomeric DNA sequences to the ends of DNA molecules. Another alternative method employs enzymes that exchange DNA sequence information between chromosomes. By one mechanism or other, cancer cells maintain telomeric length above a critical threshold and thereby retain the capacity to divide indefinitely. 

Defects in signaling pathways, cell cycle controls, and apoptosis contribute to uncontrolled proliferation.

Cell proliferation is regulated by protein growth factors that bind to cell surface receptors and activate signaling pathways within the targeted cells. While cells do not usually divide unless they are stimulated by the proper growth factor, cancer cells circumvent this restraining mechanism through alterations in signaling pathways that create a constant signal to divide. 

Normal cells become arrested at the restriction point that controls the progression from G to S phase under suboptimal conditions. However, cancer cells continue to proliferate, escaping this point. if conditions are extremely adverse, they will eventually die at random points in the cell cycle rather than arresting in G1. This abnormal behavior occurs because cell cycle controls do not function properly in cancer cells. Cancer cells are also unresponsive to internal conditions, such as DNA damage.

Cancer cells have various ways of blocking the pathways that trigger apoptosis; this allows them to survive and proliferate under conditions that would normally cause death. 

Urothelial carcinoma