The Biology of Cancer - Vibrational Spectroscopy for Tissue Analysis - page 50

the ability of invading other tissues results from having cancer cells mixed
with other types of cells in pathologic samples [3].
A difference between normal cells and cancer cells is that many cancer cells
have reduced requirements for extracellular growth factors. The growth fac-
tor requirements of many tumour cells are reduced compared to their nor-
mal counterparts, contributing to the unregulated proliferation of tumour
cells both in vitro and in vivo. In some cases, cancer cells produce growth
factors that stimulate their own proliferation. Such abnormal production of a
growth factor leads to continuous autostimulation of cell division ( autocrine
growth stimulation ), and cancer cells are therefore less dependent on growth
factors.
In some cases, the reduced growth factor dependence of cancer cells results
from abnormalities in intracellular signaling systems, such as unregulated
activity of growth factor receptors or other proteins (e.g., protein kinases) [7].
A single cell often possesses a variety of different receptors [18]. The first step
in this pathway involves the association of the ligand with the appropriate
receptor [9].
The uncontrolled proliferation of cancer cells in vivo is mimicked by their
behavior in cell culture. A primary distinction between cancer cells and
normal cells in culture is that normal cells display density-dependent inhibi-
tion of cell proliferation. Normal cells stop growing when they become over-
crowded [3] and proliferate until they reach a finite cell density, which is
determined in part by availability of growth factors added to the culture
medium (usually in the form of serum). They then cease proliferating and
become quiescent, arrested in the G 0 stage of the cell cycle. The proliferation
of most cancer cells, however, is not sensitive to density-dependent inhibi-
tion. Rather than responding to the signals that cause normal cells to cease
proliferation and enter G 0 , tumour cells generally continue growing to high
cell densities in culture, mimicking their uncontrolled proliferation in vivo
[7]. In addition, most normal cell types in the animal are attached to a struc-
tured network secreted by the cells, called the extracellular matrix . These cells
usually need to attach to a surface (such as a plastic or a glass) in order to
grow in culture. In contrast, many cancer cells can grow in culture even if
they are not attached to a surface [3].
Cancer cells are also less stringently regulated than normal cells by cell-
cell and cell-matrix interactions. Most cancer cells are less adhesive than nor-
mal cells, often as a result of reduced expression of the cell surface adhesion
molecules. For example, loss of E-cadherin, the principal adhesion molecule
of epithelial cells, is important in the development of carcinomas (epithelial
cancers). As a result of reduced expression of cell adhesion molecules, cancer
cells are comparatively unrestrained by interactions with other cells and tis-
sue components, contributing to the ability of malignant cells to invade and
metastasize [7].
A striking difference in the cell-cell interactions by normal cells and those
of cancer cells is illustrated by the phenomenon of contact inhibition . Not only