Question

Relate the properties of cell differentiation to the development of a cancer cell clone and the behavior of the tumor

Answer 1

Cell differentiation is normally an orderly process that progress from a state of immaturity to a state of maturity. Because all body cells are derived from the ferilized ova, all cells have the potential to perform all body functions. As cells differentiates, this potential is repressed and the mature cell is capable of performing only specific functions. With cell differentiation, there is a stable and orderly phasing out of cell potential. Under normal conditions, the cell did not dedifferniate

Cancer involves the malfunction of genes that control differentiation and proliferation. Two types of normal genes that can be affected by mutation

Protooncogenes: Normal cell genes that are important regulators of normal cell processes. They promote growth

Tumour Suppressor genes: suppresses the growth

Mutations that alter the expressions of protooncogenes can activate them to function as oncogenes.

The protooncogene has been described as the genetic lock that keeps the cell in its mature functioning state. when this"lock" is "unlocked", as may occur with exposure to carcinogens or oncogenic virus, genetic alterations and mutations occur. The abilities and expressions that the cell had in fetal development are again expressed. Oncogene can change a normal cell to a malignant one.These cells regain a fetal appearance and function. For eg: some cancer cells produce new proteins, such as those characterstics of embryonic and fetal periods of life. These proteins, located on the cell membranes include Carcino Embryogenic Antigen (CEA) and alpha feto protein(AFP), which can be detected in human blood by laboratory studies.

Other Cancer cells, such as  small cell carcinoma of lung , produce hormones that are ordinarily produced by cells arising from the same embryonic cells as the tumour cells

Tumour suppressor genes function to regulate cell growth. They prevent cells from going through the cell cycle. Mutations that alter tumour suppressor genes make them inactive, resulting in a loss of their tumor-suppresing action

Examples of Tumour suppressor genes are:

• BRCA1 and BRCA2. Alterations in these genes increase a person's risk for ovarian and breast cancer
• Another tumor suppressor gene is the APC gene.Alterations in this genes increase a person's risk for colorectal cancer
• Mutations in p53 tumor suppression genes have been found in many cancers, including bladder, breast, colorectal,esophageal, liver,lung and ovarian cancers

Development of cancer

Cancer occurs through an orderly process and occurs overtime and has several stages

• Initiation
• Promotion
• progression

Initiation

Cancer cells arise from normal cells as a result of changes in genes.It involves mutation in the cell's genetic structure. Gene mutations can occur in two ways:

Inherited from a parent

Acquired during a person's life time

Carcinogens are known to cause acquired cancer

Chemical carcinogens such as certain chemicals , drugs such as alkylating agents(eg: cyclophoshamide) is associated with an increased incidence of NonHodghkin's Lymphoma,multiple myeloma and Hodghkin's lymphoma

Radiation: can cause cancer in any body tissue

Ex: Leukemia, lymphoma,thyroid cancer and other cancers are common in Hiroshima after atomic bomb explosion

A higher incidence of bone cancer occur in people exposed to radiation such as radiologists,radiation chemists and uranium miners

UV rays are associated with melanoma,squamous and basal cell carcinoma of the skin

Viral carcinogens: HIV, Hepatitis B virus, Humanpappiloma virus, ebstien barr virus are associated with cancers of head,neck,cervix

Promotion

Reversible proliferation of altered cells

promoting factors include:

• Dietary fat
• Obesity
• Cigarette smoking
• Alcohol consumption

An important distinction between initiation and promotion is that promotion is reversible and preventable. This is a key concept in cancer prevention

Cigarette smoke is a promoting agent in bronchogenic carcinoma, and in conjunction with alcohol intake promotes esophageal nd bladder cancer

Progression

Is the final stage and is characterized by the increase growth rate of the tumor, increased invasiveness and metastasis (spread of cancer to distant site)

Colon cancer usual sites for metastasis is liver

Melanoma- unpredictable in the pattern of metastasis. Usual sites are lungs, liver, bone, brain and adrenal glands

Metastasis is a multi-step process beginning with rapid growth of primary tumour. As the tumour increases in size, development of blood vessels within the tumour occurs and is termed as tumour angiogenesis