Introduction of cancer

Cancer claims one of the top ten causes of death in Taiwan in the recent years. Cancer is characterized by the lack of apparent symptoms in its early stages, and that treatments for cancer can be difficult and ineffective. All cancers begin in cells. Normal body cells undergo controlled growth and divisions, expressed by their genetic materials, to form functional tissues and organs. The different types of cells in the body, including intestinal mucous cells, epithelial cells of skin, and hematopoietic precursor cells in bone marrow, continuously proliferate, divide, grow, die and replaced as they become old or damaged. However, loss of normal growth control could happen when mutations occur in DNA due to genetic problems or environmental risk factors such as infections, radiations, and carcinogens. In fact, mutations occur regularly in normal controlled cell division but these mutated cells quickly undergo apoptosis before turning into tumor cells. Once the bodies lose control of cell division, mutated cells could proliferate indefinitely, and directly invade neighbouring tissues or spread to other organs through the lymph system and vascular networks.

Moreover, tumor cells continuous to grow uncontrollably when they reach distal organs, where they damage the tissues and functions of the organs and lead to complications.

1.2.1 Differences between cancer and normal cells

Tumor cells stems from normal cells, however several major differences exist between the two:

1) Cell Structure: Under normal condition, regular cells from the same tissue have relatively the same size and shape, however, tumor cells originate from a tissue are much bigger than a normal cell of the same tissue because the nucleus of a tumor cell is bigger and of a different shape. In addition, cases of giant nuclei, multiple nuclei, or distorted nuclei are also possible.

2) Cell Growth: The growth of tumor cells has two characteristics a) Autonomous growth: Under normal cell growth, divisions cease when the proliferating cells come in contact with another cell. On the other hand, tumor cells continue to proliferate and divide abnormally at a higher growth rate without control, thereby growing on top of each other or erode into the surrounding tissue.

b) Metastasis: A tumor can be non-cancerous or cancerous, differentiated by cancerous cells' ability to metastasize and erode

into the surrounding structure, because the motility of normal cells are limited by the adhesive force existing between them. The ability of cancerous cells to migrate to nearby and distal locations is due to the loss of adhesive force between cells as a result of structural change on cell surfaces, which cause the cancerous cells to erode surrounding tissue and travel to different parts of the body through blood and lymphatic vessels.

3) Cell Metabolism: Metabolism is necessary to keep a cell alive and functional. However, a great difference in metabolic rate is found between a normal and tumor cell, especially in protein and nucleic acid synthesis. Protein synthesis is increased in tumor cell, while the breakdown of protein is slowed, leading to an imbalance between the rate of protein synthesis and degradation.

4) Malignity and Heredity: Tumor cells have higher malignity and growth rate, and most are capable of metastasis since early stages of cancers, hence cancers are often difficult to cure. Furthermore, tumor cells can pass down their ability of autonomous growth to the next generation of tumor cells, producing proliferating cells of the same malignant characteristics.

1.2.2 Metastasis of cancer cells

Traditionally, metastasis of cancerous cells is thought to occur only during later stages of tumor growth. However, the recent research suggests that most of tumor cells are already capable of metastasis during the early stages. In other words, migration to distal sites could happen during early stages of tumor formation.

Many recent findings indicate that non-cancerous and cancerous tumor cells do not share exactly the same genetic materials or characteristics. In general, there are two routes of metastasis:

a) Lymphatic spread is one route of metastasis, where the tumor cells proliferate at regional lymph nodes and the invasion eventually becomes clinically detectable. Towards the later stages of cancers, some of the tumor cells at the lymph nodes may be cancerous cells, which then metastasize to other parts of the body through the lymphatic system, leading to tumor formations at distal sites such as the head and neck.

b) Haematogenous spread is another route of metastasis, and it occurs during the early stages of cancers through blood vessels.

Tumor cells may reach any part of the body, even bone marrows,

but these tumor cells have short life span and do not have the capacity for rapid proliferation. However, a small number of the metastasized tumor cells could still have rapid growth rate, therefore a second metastasis is possible. An example of cancer as a result of haematogenous spread is breast cancer.

Beside metastasizing into neighbouring tissue, cancerous cells at the site of origin are even more malignant and have began metastasizing much earlier through blood capillary network or lymphatic vessels to regional lymph nodes or other organs.

However, metastasis requires several steps to complete, including:

1) Cancerous cells are nourished by self-generating autocrine factors as well as the paracrine factors produced by surrounding tissues.

2) When the diameter of a cancerous cell has increased to 1-2 millimeters, it will become dependent on the formation of capillary networks around the tumor for nourishment and growth. At this point, some of the tumor cell adhesion molecules would undergo negative regulation, thereby encouraging cell fluidity and detachment from the site of origin into surrounding blood circulations.

3) Cancerous cells metastasize through blood capillaries into other body parts including, lungs, liver, and bones. There are receptors on the surface of the cancerous cells that react with the paracrine signals from various organs, providing these cancerous cells with sufficient nutrients for continuous growth.

4) Therefore, most clinical cases of metastasis are of multiple metastatic lesions, where the cancerous cells are heterogeneous in gene expressions. The trend for future research in cancer treatment should then be finding out the specific genetic properties of the metastasising cells and formulating a targeted therapy.