The human body encompasses some thirty trillion cells. The cells which comprise normal, healthy tissues in the body live in an interdependent relationship with surrounding cells. These tissues are intricately arranged into a marvelous array of cell to cell adhesions and extracellular matrixes. Healthy cells reproduce in a coordinated manner which insures that a particular body tissue maintains its appropriate size, form, and function. Cells which have lost the ability to reproduce in a controlled fashion are termed cancerous cells. Cancer cells proliferate uncontrollably forming tumors causing disruption in the normal form and function of body tissues. The most dangerous of the cancer cells are those that can metastasize, which is the ability of the cell to migrate from the original or primary tumor site to a distant site where they establish secondary tumors. This is what makes metastasizing cancer cells so lethal and distinguishes a malignant cancer from a non-malignant cancer.
Migrating Cancer Cell in vitro
In order to accomplish such a migration, the malignant cells need to proceed through a series of steps which include:
1. detachment from the primary tumor mass
2. degradation of the basement membrane
3. migration to and invasion of a nearby blood or lymphatic vessel
4. survival within the blood or lymph system
5. attachment to the wall of the vessel at some distant site
6. penetration of the vessel wall and exiting of the vessel
7. migration to a site where a secondary tumor is established.
The Role of Anchorage Dependence in Metastasis
The mechanisms involved in the survival of a cell detached from the extracellular matrix are of great interest. Normal cells are anchorage dependent and are designed to commit "suicide" if detached from cells of their own kind. This is a measure that prevents cancer and other abnormal growths from arising in most cases. A summary of how a cell can avoid anchorage dependence follows. A cancerous cell begins as a normal cell anchored to the extracellular matrix. Proto- oncogenes in the cell are mutated into oncogenes. The cell is able to break away from the extracellular matrix and integrins send messages to the nucleus that the cell is no longer attached to the matrix. The messages are ignored because of the messages the nucleus receives as a result of the mutant oncogenes. E-CDK2 continues to be produced at normal levels, preventing the cell from undergoing apoptosis. The cell floats towards the basement membrane which it permeates by emitting metalloproteinases on its way to the blood vessel.
The nucleus will be informed of detachment from the extracellular matrix by the integrins. E-CDK2 production will lower significantly. A normal cell will undergo apoptosis, cell suicide, if the cell is detached from the matrix.
A cancerous cell will be able to survive without being attached to other cells. This means that it can grow and...