15 Glycolytic Oscillations in Cancer Cells
253
15.8 Conditions for Glycolytic Oscillations in Cancer Cells
Experiments indicated that the ratio of oscillatory cells was higher under both glucose
and serum starved condition (Glc−, FBS−) than under only glucose starved condition
(Glc−, FBS+) [5]. This was also reproduced by our mathematical model, which
assumed that the values of rate constants of glycolytic enzymes were lower under
the former condition (Glc−, FBS−) than under the latter (Glc−, FBS+). The above
consideration is reasonable because both glucose and serum starvation are reported
to decrease the glycolytic enzymatic activities in cancer cells [10, 29, 64, 67]. In
contrast, glucose starvation induces increase in the glucose uptake rate in HeLa cells
[53]. Thus, it can be said that cancer cells tend to exhibit more glycolytic oscillations
with lower activities of glycolytic enzymes and higher velocities of glucose uptake.
This was represented by our mathematical model under conditions of glucose and
serum starvation (Glc−, FBS−) and glucose starvation (Glc−, FBS+) in our previous
study [4].
Thus, we numerically examined the oscillatory conditions as functions of the
activities of glycolytic enzymes (α), and the maximum velocity of glucose uptake
(V max ); Based on these results we proposed a schematic model in Fig. 15.5. Here, a
parameter α was introduced in our model [4], and has linear relationships with the
Fig. 15.5 Schematic of steady-state (SS) and oscillatory (OSC) regions spanned by enzymatic
activity, α, and maximum rate of glucose uptake, V max , through glucose transporter as shown in
Fig. 15.4. This graph is drawn on the basis of numerical calculations of SS and OSC behaviours
using the mathematical model (Fig. 15.4). We can see that cancer cells tend to oscillate more
with lower enzymatic activity and higher glucose-uptake rate. Populations of three types of cancer
cells, prostate, cervical, and pancreatic cancers, are indicated in the diagram by circles. These cells
may exhibit glycolytic oscillations under pre-incubation without glucose (glucose-starvation); the
oscillatory cells are indicated by the coloured region. On the basis of our studies of glycolytic
oscillations in HeLa cervical and DU145 prostate cancer cells, and literature survey, we postulated
that more malignant cancer has higher glycolytic enzymatic activity and glucose-uptake rate
253
15.8 Conditions for Glycolytic Oscillations in Cancer Cells
Experiments indicated that the ratio of oscillatory cells was higher under both glucose
and serum starved condition (Glc−, FBS−) than under only glucose starved condition
(Glc−, FBS+) [5]. This was also reproduced by our mathematical model, which
assumed that the values of rate constants of glycolytic enzymes were lower under
the former condition (Glc−, FBS−) than under the latter (Glc−, FBS+). The above
consideration is reasonable because both glucose and serum starvation are reported
to decrease the glycolytic enzymatic activities in cancer cells [10, 29, 64, 67]. In
contrast, glucose starvation induces increase in the glucose uptake rate in HeLa cells
[53]. Thus, it can be said that cancer cells tend to exhibit more glycolytic oscillations
with lower activities of glycolytic enzymes and higher velocities of glucose uptake.
This was represented by our mathematical model under conditions of glucose and
serum starvation (Glc−, FBS−) and glucose starvation (Glc−, FBS+) in our previous
study [4].
Thus, we numerically examined the oscillatory conditions as functions of the
activities of glycolytic enzymes (α), and the maximum velocity of glucose uptake
(V max ); Based on these results we proposed a schematic model in Fig. 15.5. Here, a
parameter α was introduced in our model [4], and has linear relationships with the
Fig. 15.5 Schematic of steady-state (SS) and oscillatory (OSC) regions spanned by enzymatic
activity, α, and maximum rate of glucose uptake, V max , through glucose transporter as shown in
Fig. 15.4. This graph is drawn on the basis of numerical calculations of SS and OSC behaviours
using the mathematical model (Fig. 15.4). We can see that cancer cells tend to oscillate more
with lower enzymatic activity and higher glucose-uptake rate. Populations of three types of cancer
cells, prostate, cervical, and pancreatic cancers, are indicated in the diagram by circles. These cells
may exhibit glycolytic oscillations under pre-incubation without glucose (glucose-starvation); the
oscillatory cells are indicated by the coloured region. On the basis of our studies of glycolytic
oscillations in HeLa cervical and DU145 prostate cancer cells, and literature survey, we postulated
that more malignant cancer has higher glycolytic enzymatic activity and glucose-uptake rate