Biomedical Engineering Reference
In-Depth Information
inhibition is controlled by anchorage-dependent growth and maintenance. If a
society sends out an individual to explore who is ill-equipped, that explorer will
likely perish. If a normal cell becomes disconnected from its neighbors or the
basement membrane that it resides on, apoptosis is triggered and the cell dies.
Cancer cells have acquired mutations that allow them to grow independent of
attachment to a basement membrane or to other cells (27-29). This anchorage
independence releases the cell from communicating with its neighbors and
breaks down the fundamental fidelity of the organism system. Several cell at-
tachment proteins have been identified that have been demonstrated to be altered
in cancer cells. These mutations also allow the cancer cell the freedom to leave
the primary tumor environment and start down the path of metastasis (30).
3.5. Ability to Ensure a Nutrient Supply
A group of cancer cells undergoing clonal expansion can only become ap-
proximately a cubic millimeter in size (20 population doublings, one million
cells) without a blood supply to oxygenate the cells (31). A critical step in suc-
cessful cancer development is the release of factors such as vascular endothelial
growth factor (VEGF) from the cancer cells to attract new blood vessel growth
(neovascularity of angiogenesis) (32,33). This is a good example of how cancer
cells, even in the presence of tumor cell heterogeneity, must unconsciously co-
operate with each other. No single cell produces enough VEGF to stimulate the
growth of a new blood supply by itself. Enough individual cells or clones must
then have the ability to each secrete VEGF into the surrounding environment to
allow a gradient of growth factor to be established to attract new blood vessels.
3.6. Population Expansion and Growth beyond Natural Boundaries
Cancer rarely kills its host because of its growth in one single organ. The
majority of such cancers can be successfully treated by surgery and/or radiation.
Even untreated, a solitary cancer can grow in a primary organ for years before
becoming clinically evident. Cancer kills because it spreads (metastasizes) to
other organs. This certainly requires the mutations that allow uncontrolled
growth, anchorage independent growth, apoptosis evasion, and new blood vessel
growth. But it also requires the acquisition of several other adaptation proper-
ties. Even though the cancer cell does not require its neighbors to grow, to be
lethal it has to acquire properties that allow it to leave the primary tumor envi-
ronment. For the cancer cell population to grow, it must break down its sur-
rounding tissue environment. This periphery of the tumor is the most
oxygenated and has the richest nutrient gradients. For the cancer cells to keep
expanding into this environment, there must be a selective pressure for cells that
can invade into that environment. It has been demonstrated that cancer cells se-
crete high amounts of proteases that break down the confining extracellular ma-
trix of surrounding tissue (34). This allows continued growth of the clonal
