MATHEMATICAL MODELS ON THE GROWTH OF SOLID TUMORS - Quantitative Medical Data Analysis Using Mathematical Tools and Statistical Techniques - page 301

fects. Spencer et al 65 foresee cancer research developing into logical sci-
ences, where the molecular and clinical complexities of the disease will be
understood in terms of a few underlying principles.
4. Experiments
4.1. MTS experiments
Multicellular tumor spheroid (MTS) experiments as an in vitro tumor
model can provide data on the duration of the cell cycle, growth rate,
chemical diusion, etc 26;27 .
Tumor growth requires the transport of nutrients, for example oxy-
gen, and glucose, from and waste products to the surrounding tissue.
These nutrients regulate cell mitosis, cell death, and potentially cell mu-
tation. MTS experiments have the great advantages of precisely control-
ling the external environment while maintaining the cells in the spheroid
microenvironment 27;28 . Suspended in culture, tumor cells grow into a
spheroid, in a process that closely mimics the growth characteristics of
early stage tumors. MTS exhibits three distinct phases of growth:
(1) an initial phase during which individual cells form small clumps that
subsequently grow quasi-exponentially;
(2) a layering phase during which the cell-cycle distribution within the
spheroids changes, leading to formation of a necrotic core, accumulation
of quiescent cells around the core, and sequestering of proliferating cells
at the periphery; and
(3) a plateau phase during which the growth rate begins to decrease and
the tumor ultimately attains a maximum diameter.
In order to understand the underlying dynamics of cell growth within a
spheroid, Chandrasekar et al. 19 studied the spatial-temporal distribution
of the cells spheroids cultured from cell line. They found that the size of
the spheroids and their growth rates were dependent on the cell number,
the proliferation was mostly limited to out most region as the spheroids
grew in size, and the number of dead cells increased with age and size as
well.
Mechanical eects from the surrounding environment as well as that
generated internally by cellular growth play an important role in regulat-
ing tumor growth. Evidence that cell stress aects proliferation is provided
by Helmlinger et al. 34 . By culturing spheroids in gels of dierent stiness, it
was demonstrated that the stress exerted on tumor cells by their surround-