Biomedical Engineering Reference
In-Depth Information
ing aects its equilibrium size. High stress is observed to down-regulate cell
proliferation and promote cell death
38
.
5. Extracellular scale models
The macroscopic (extracellular) scale refers to phenomena which are typical
of continuum systems: cell migration, convection, diusion (of chemical
factors, nutrients), phase transition (from free to bound cells and vice versa)
detachment of cells and formation of metastases, and so on. The avascular
stage of growth is characterized by:
(i) Small and occult lesions (1-2mm in diameter),
(ii) Formation of a necrotic core of dead tumor cells where a process of
destroying cellular debris may take place,
(iii) Formation of an outer region of proliferating tumor cells and of an
intermediate region of quiescent cells,
(iv) Production of chemical factors, among which several growth inhibitory
factors, generally called GIF, and growth promoting factors, called
GPF, by the tumor mass, thus controlling the mitosis,
(v) Dependence of the tumor cells mitotic rate on the GIF and GPF con-
centration,
(vi) Non-uniformities in the proliferation of cells and in the consumption of
nutrients, which lter through the surface of the spheroid and diuse
in the intracellular space.
Since at this stage the tumor is not surrounded yet by capillaries, this phase
can be observed and studied in laboratory by culturing cancer cells. On the
other hand, the tumor angiogenic phase is characterized by:
(i) Secretion of tumor angiogenesis factors promoting the formation of new
blood vessels (VEGF, FGF and others) as described in Bussolino et al.
13
(ii) Degradation of basement membrane by several enzymes. Endothelial
cells are then free to proliferate and migrate towards the source of the
angiogenic stimulus,
(iii) Recruitment of new blood vessel that supply the tumor (neovascular-
ization) and increase of tumor progression,
(iv) Aberrant vascular structure, abnormal blood ow, with continuous
growth of new tumor blood vessels.
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