The Biology of Cancer - Vibrational Spectroscopy for Tissue Analysis - page 49

Disordered Mechanisms in Malignant Cells
Whatever the reason for cell mutations, there are at least four mechanisms
that might become disordered in malignant cells and result in aberrant pro-
liferation [9]:
1. Abnormalities in growth factor production
2. Abnormalities in growth factor receptors
3. Disturbances of postreceptor signaling
4. The reduced production of or sensitivity to growth inhibiting factors
In fact, the proliferation and differentiation of all mammalian cells is gen-
erally controlled by extracellular signals, which are referred to as peptide
regulatory factors (PRFs). They include platelet-derived growth factor (PDGF),
epidermal growth factor (EGF), nerve growth factor (NGF), transforming
growth factor α (TGFα), and fibroblast growth factor (FGF). More recently,
glycoproteins produced by activated T cells (lymphokines), monocytes, and
macrophages (monokines) have been added to this list, including the inter-
leukins (IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, and IL-10), granulocyte macrophage
colony stimulating factor (GM-CSF), granulocyte colony stimulating factor
(G-CSF), the interferons (INFs α and µ), tumour necrosis factor (TNF), and
lymphotoxin. These molecules may mediate both the immune and inflam-
matory responses as well as constitutive haematopoiesis. In addition,
other factors produced by stromal cells, e.g., M-CSF (CSF-1), IL-7, leukemia
inhibitory factor (LIF), and stem cell factor (SCF) form a group of molecules
called cytokines . At least 40 cytokines are known to act on the haemopoietic
system [3,7,9,18].
Cancers escape control by their environment through having (i) decreased
sensitivity to inhibitory signals from adjacent cells and the extracellular
matrix, or (ii) decreased requirement for growth stimulatory factors. They
can either produce more ligand or become independent of the ligand [5]. As
mentioned, apart from the property of invading other tissues and organs,
cancer cells attain a degree of autonomy from external regulatory signals [3].
This specification renders these cells less subject to such signals than nor-
mal cells. This autonomy is reflected in a lower requirement for growth
stimulatory molecules and a diminished sensitivity to inhibitory signals
provided by adjacent cells and the extracellular matrix. These stimulatory
and inhibitory extracellular stimuli are recognized by receptors and con-
veyed to the nucleus by complex multiple pathways. The altered activity is
directed, obtains a growth advantage over adjacent cells, and is achieved by
increasing the efficiency of the intracellular machinery directed at prolifera-
tion and by production secreted growth factors [5]. It must be mentioned that