15 Glycolytic Oscillations in Cancer Cells
255
prostate cancer has very high five-year survival rates, cervical cancer has moderate
survival rates, and pancreatic, liver, and lung cancers have very low survival rates
in other countries [1, 50]. Naturally, five-year cancer survival rates are affected by
earlier detection and/or improved treatment, nonetheless it can be considered to be
a good indicator representing malignancy of cancer.
Based on the above considerations, three types of cancer, i.e., pancreatic, cervical,
and prostate cancers, are schematically plotted in the diagram (Fig. 15.5). In the
diagram, populations of more malignant cancer are located in more upper right
region. Upon addition of glucose after glucose starvation, or glucose and serum
starvation, a certain number of these cancers may exhibit glycolytic oscillations. We
hypothesise from the studies of HeLa and DU145 cells that more malignant cancer
may exhibit higher oscillatory ratio. More studies using various types of cancer cells
are necessary in order to verify this hypothesis regarding the relationship between
malignancy and characteristics in glycolytic oscillations in cancer cells, which will
be applied for diagnosis of cancer.
15.10 Summary
Fifty years after the discovery of glycolytic oscillations in Ehrlich ascites tumour cells
grown in suspension, the individual and collective behaviours have been unravelled
in HeLa cells due to the advancements in experimental and analytical techniques.
Strong heterogeneities were found in their glycolytic oscillations, indicating that
glycolytic enzymatic activities are very heterogeneous in HeLa cells. Furthermore,
the degree of synchronisation in the oscillations was very low, indicating very little
cell-to-cell interaction during glycolysis in HeLa cells. Nearly the same qualitative
behaviours were also observed in DU145 cells.
Based on the experiments of glycolytic oscillations in HeLa and DU145 cells, and
the literature available on glycolytic activities and malignancy in cancer cells, we have
proposed a model indicating the relationship between malignancy of cancer cells and
their glycolytic oscillation characteristics. We propose that more malignant cancer
cells tend to exhibit glycolytic oscillations with shorter periods than less malignant
cells. Thus, glycolytic oscillations in cancer cells may be a medical indicator to detect
the malignancy of cancer cells.
Acknowledgements We are grateful to Professor Stefanovska for useful discussions on glycolytic
oscillators. This study was supported in part by a grant for Cooperative Research Project to T. A. from
YNU, JSPS KAKENHI Grant Numbers 17KT0123 to S. N., 19H04205 to T. A., MIMS/CMMA
collaborative research symposium to T. Y. and T. A., MIMS Joint Research Project for Mathematical
Sciences to T. Y, Health Labour Science Research Grant to M. W., and JST PRESTO JPMJPR1774
to K. N. We would like to thank Editage (www.editage.com) for English language editing.
255
prostate cancer has very high five-year survival rates, cervical cancer has moderate
survival rates, and pancreatic, liver, and lung cancers have very low survival rates
in other countries [1, 50]. Naturally, five-year cancer survival rates are affected by
earlier detection and/or improved treatment, nonetheless it can be considered to be
a good indicator representing malignancy of cancer.
Based on the above considerations, three types of cancer, i.e., pancreatic, cervical,
and prostate cancers, are schematically plotted in the diagram (Fig. 15.5). In the
diagram, populations of more malignant cancer are located in more upper right
region. Upon addition of glucose after glucose starvation, or glucose and serum
starvation, a certain number of these cancers may exhibit glycolytic oscillations. We
hypothesise from the studies of HeLa and DU145 cells that more malignant cancer
may exhibit higher oscillatory ratio. More studies using various types of cancer cells
are necessary in order to verify this hypothesis regarding the relationship between
malignancy and characteristics in glycolytic oscillations in cancer cells, which will
be applied for diagnosis of cancer.
15.10 Summary
Fifty years after the discovery of glycolytic oscillations in Ehrlich ascites tumour cells
grown in suspension, the individual and collective behaviours have been unravelled
in HeLa cells due to the advancements in experimental and analytical techniques.
Strong heterogeneities were found in their glycolytic oscillations, indicating that
glycolytic enzymatic activities are very heterogeneous in HeLa cells. Furthermore,
the degree of synchronisation in the oscillations was very low, indicating very little
cell-to-cell interaction during glycolysis in HeLa cells. Nearly the same qualitative
behaviours were also observed in DU145 cells.
Based on the experiments of glycolytic oscillations in HeLa and DU145 cells, and
the literature available on glycolytic activities and malignancy in cancer cells, we have
proposed a model indicating the relationship between malignancy of cancer cells and
their glycolytic oscillation characteristics. We propose that more malignant cancer
cells tend to exhibit glycolytic oscillations with shorter periods than less malignant
cells. Thus, glycolytic oscillations in cancer cells may be a medical indicator to detect
the malignancy of cancer cells.
Acknowledgements We are grateful to Professor Stefanovska for useful discussions on glycolytic
oscillators. This study was supported in part by a grant for Cooperative Research Project to T. A. from
YNU, JSPS KAKENHI Grant Numbers 17KT0123 to S. N., 19H04205 to T. A., MIMS/CMMA
collaborative research symposium to T. Y. and T. A., MIMS Joint Research Project for Mathematical
Sciences to T. Y, Health Labour Science Research Grant to M. W., and JST PRESTO JPMJPR1774
to K. N. We would like to thank Editage (www.editage.com) for English language editing.