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T. Amemiya et al.
values of four rate constants (k 1 –k 4 ) of glycolytic enzymes in the model. We can see
that more glycolytic oscillations tend to occur with lower enzymatic activities and
the higher velocity of glucose uptake as mentioned above.
Effects of starvation of glucose, or both glucose and serum on the oscillations are
represented in the diagram (Fig. 15.5). Cancer cells with no-starvation of glucose,
(Glc+, FBS+) and serum starved cells (Glc+, FBS−), exhibited no glycolytic oscillations upon addition of glucose, thus the population of cells is schematically indicated
by a white-outlined circle in a steady-state region (SS) in the diagram. Glucosestarvation is reported to decrease the activities of glycolytic enzymes [64, 67] and
also to increase the velocity of glucose uptake [53]. On the other hand, serumstarvation is reported to decrease enzymatic activities [10, 29]. Thus, starvation of
both glucose and serum totally moves the population of cells to a region indicated
by a partly coloured circle where some of the cells are in an oscillatory state (OSC).
The oscillatory ratio can change depending on starvation conditions and on the type
of cells.
15.9 Malignancy of Cancer Cells and Glycolytic
Oscillations
Based on previous studies of glycolytic oscillations in HeLa cells [4, 5], and DU145
cells presented here, and the characteristics of glycolytic activities in cancer cells as
will be mentioned below, we assume that the greater the malignancy of cancer cells,
the more they tend to exhibit glycolytic oscillations. Thus our operating definition of
malignancy of cancer cells with relation to cellular metabolism is that more malignant
cancer cells may enhance more glycolytic activities.
Multiple glycolytic enzymes are highly expressed in various types of cancers,
including pancreatic cancer [65], one of the most malignant cancers, and promote
metastasis [2]. By comparing two breast cancer cell lines MCF7 and MDA-MB231,
highly invasive MDA-MB231 cells were reported to be more glycolytic than noninvasive MCF7 cells [20, 46]. With regard to adoptive T cell therapy, increased
tumour glycolytic activity is shown to be associated with lower therapeutic response,
and glycolysis-related genes are reported to be upregulated in melanoma and lung
cancer patient samples that are poorly infiltrated by T cells [11]. Further, glucosetransporter 1 (GLUT1) is also reported to be highly expressed in tumour cell lines
of different organs such as renal cell carcinoma, melanoma, and hepatocellular
carcinoma compared to their non-malignant counterparts [56].
However, according to worldwide epidemiological survey [50], prostate cancer,
whose cell line (DU145) exhibited little glycolytic oscillations in our study
(Fig. 15.3), was reported to have close to 99% five-year survival rates in 2013,
in the US; in contrast, pancreatic cancer showed very low five-year survival rates of
8.2%. Cervical cancer, whose cell line (HeLa) exhibited glycolytic oscillations [5],
was reported to have five-year survival rates of 67% in 2009 in the US. In general,
T. Amemiya et al.
values of four rate constants (k 1 –k 4 ) of glycolytic enzymes in the model. We can see
that more glycolytic oscillations tend to occur with lower enzymatic activities and
the higher velocity of glucose uptake as mentioned above.
Effects of starvation of glucose, or both glucose and serum on the oscillations are
represented in the diagram (Fig. 15.5). Cancer cells with no-starvation of glucose,
(Glc+, FBS+) and serum starved cells (Glc+, FBS−), exhibited no glycolytic oscillations upon addition of glucose, thus the population of cells is schematically indicated
by a white-outlined circle in a steady-state region (SS) in the diagram. Glucosestarvation is reported to decrease the activities of glycolytic enzymes [64, 67] and
also to increase the velocity of glucose uptake [53]. On the other hand, serumstarvation is reported to decrease enzymatic activities [10, 29]. Thus, starvation of
both glucose and serum totally moves the population of cells to a region indicated
by a partly coloured circle where some of the cells are in an oscillatory state (OSC).
The oscillatory ratio can change depending on starvation conditions and on the type
of cells.
15.9 Malignancy of Cancer Cells and Glycolytic
Oscillations
Based on previous studies of glycolytic oscillations in HeLa cells [4, 5], and DU145
cells presented here, and the characteristics of glycolytic activities in cancer cells as
will be mentioned below, we assume that the greater the malignancy of cancer cells,
the more they tend to exhibit glycolytic oscillations. Thus our operating definition of
malignancy of cancer cells with relation to cellular metabolism is that more malignant
cancer cells may enhance more glycolytic activities.
Multiple glycolytic enzymes are highly expressed in various types of cancers,
including pancreatic cancer [65], one of the most malignant cancers, and promote
metastasis [2]. By comparing two breast cancer cell lines MCF7 and MDA-MB231,
highly invasive MDA-MB231 cells were reported to be more glycolytic than noninvasive MCF7 cells [20, 46]. With regard to adoptive T cell therapy, increased
tumour glycolytic activity is shown to be associated with lower therapeutic response,
and glycolysis-related genes are reported to be upregulated in melanoma and lung
cancer patient samples that are poorly infiltrated by T cells [11]. Further, glucosetransporter 1 (GLUT1) is also reported to be highly expressed in tumour cell lines
of different organs such as renal cell carcinoma, melanoma, and hepatocellular
carcinoma compared to their non-malignant counterparts [56].
However, according to worldwide epidemiological survey [50], prostate cancer,
whose cell line (DU145) exhibited little glycolytic oscillations in our study
(Fig. 15.3), was reported to have close to 99% five-year survival rates in 2013,
in the US; in contrast, pancreatic cancer showed very low five-year survival rates of
8.2%. Cervical cancer, whose cell line (HeLa) exhibited glycolytic oscillations [5],
was reported to have five-year survival rates of 67% in 2009 in the US. In general,