Download Tumor growth Kinetics of tumor growth and angiogenesis

Tumor growth
Kinetics of tumor growth and angiogenesis
Angiogenesis is an important physiological process in normal
embryogenesis, the female reproductive cycle, and wound healing. However,
pathological angiogenesis is a key player in many disorders including cancer.
This is because a solid tumor cannot grow beyond a few millimeters in a
diameter without a blood supply to maintain nutrient and oxygen provision
and remove metabolic waste.
In normal cells, angiogenesis is a tightly controlled highly regulated
mechanism. In contrast, tumor cells can release pro-angiogenic factors,
which induce vascular proliferation. This is sometimes called angiogenic
switch. The angiogenic switch results in the production of pro-angiogenic
molecules such as vascular endothelial growth factor VEGF. Eventually, the
tumor may outgrow its blood supply, and areas of necrosis may appear,
resulting in slower growth but a more malignant phenotype. This is because
only the strongest cells survive the hypoxic conditions.
Mechanisms and pathways of invasion and metastasis:
The ability to invade is the only absolute criterion for malignancy. Invading
malignant cells have the following properties:
 Abnormal or increased cellular motility due to loss of contact
inhibition.
 Altered cellular adhesion due to changes in surface adhesion
molecules.
 Increased secretion of proteolytic enzymes, e.g., metalloproteinases.
Metalloproteinases, such as collagenases and gelatinases, are the most
important enzymes in neoplastic invasion. These enzymes digest the
surrounding connective tissue thus aiding invasion.
Metastasis: is the process whereby malignant cells spread from their site of
origin –primary tumor- to distant sites and grow to secondary tumors.
Total mass of secondary tumors usually exceeds that of the primary lesion.
Only a proportion of neoplastic cells in malignant tumor are able to
metastasize. It is sometimes impossible to find the primary lesion in some
cancer patients who present with extensive secondary metastases.
In order to metastasize, neoplastic cells undergo the following sequence of
events:
 Detachment of tumor cells from neighboring cells.
 Invasion of surrounding connective tissue
 Intra-vasation into blood/lymphatic vessels.
 Evasion of the host's defense mechanisms
 Adherence to endothelium at a distant site.
 Extra-vasation of cells from Vessel lumen into the surrounding tissue.
Following extra-vasation, the malignant cells proliferate and secret more
angiogenic growth factors for vascularization. Hence a new tumor is formed.
However, not all cancer cells will grow at all distant sites. This is the seed
and soil effect – conditions must be appropriate for cell proliferation.
Main routes of metastasis:
There are 4 main routes of metastasis:
1. Local invasion: most common pattern of spread of malignant tumors is
by direct growth into adjacent tissues.
2. Lymphatic spread: forms secondary tumors in lymph nodes.
3. Blood born spread: cells enter the blood stream and form secondary
tumors in organs perfused by blood that has drained from a tumor.
Common tumors that spread to bone by the blood are bronchus, breast,
thyroid, kidney, and prostate.
4. Transcoelomic spread: in pleural, pericardial, and peritoneal cavities.