Characterizing inhibited tumor growth in stem-cell-driven non-spatial cancers

Mathematical Biosciences
Ignacio A Rodriguez-BrenesNatalia L Komarova

Abstract

Healthy human tissue is highly regulated to maintain homeostasis. Secreted negative feedback factors that inhibit stem cell division and stem cell self-renewal play a fundamental role in establishing this control. The appearance of abnormal cancerous growth requires an escape from these regulatory mechanisms. In a previous study we found that for non-solid tumors if feedback inhibition on stem cell self-renewal is lost, but the feedback on the division rate is still intact, then the tumor dynamics are characterized by a relatively slow sub-exponential growth that we called inhibited growth. Here we characterize the cell dynamics of inhibited cancer growth by modeling feedback inhibition using Hill equations. We find asymptotic approximations for the growth rates of the stem cell and differentiated cell populations in terms of the strength of the inhibitory signal: stem cells grow as a power law t(1/k+1),and the differentiated cells grow as t(1/k), where k is the Hill coefficient in the feedback law regulating cell divisions. It follows that as the tumor grows, undifferentiated cells take up an increasingly large fraction of the population. Implications of these results for specific cancers including CML are discussed. Understan...Continue Reading

References

Nov 21, 1995·Proceedings of the National Academy of Sciences of the United States of America·I P Tomlinson, W F Bodmer
Jul 15, 1999·The New England Journal of Medicine·S FaderlH M Kantarjian
Jun 22, 2000·Annals of Surgery·D M SimeoneC D Logsdon
Jan 4, 2001·Nature Genetics·A DaluiskiK M Lyons
Mar 10, 2001·Journal of Theoretical Biology·L K Andersen, M C Mackey
Aug 2, 2001·Proceedings of the National Academy of Sciences of the United States of America·K L Woodford-RichensI P Tomlinson
Jan 28, 2003·Neuron·Hsiao-Huei WuAnne L Calof
Mar 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Muhammad Al-HajjMichael F Clarke
Jul 10, 2003·Journal of Theoretical Biology·Samuel BernardMichael C Mackey
Sep 25, 2003·Proceedings of the National Academy of Sciences of the United States of America·Emmanuelle PasseguéIrving L Weissman
Aug 25, 2004·Cell Cycle·Kjell Elgjo, Karl L Reichelt
Nov 3, 2004·The Journal of Membrane Biology·R ReussV L Sukhorukov
Jan 22, 2005·Annual Review of Medicine·Judith A ShizuruIrving L Weissman
Jun 25, 2005·Journal of Theoretical Biology·Caroline Colijn, Michael C Mackey
Jul 1, 2005·Nature·Franziska MichorMartin A Nowak
Oct 20, 2006·Journal of Theoretical Biology·Alberto d'Onofrio, Ian P M Tomlinson
Nov 7, 2006·Bulletin of Mathematical Biology·Mostafa AdimyShigui Ruan
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Matthew D JohnstonS Jonathan Chapman
May 23, 2008·Medical Hypotheses·Yuan LiuYan Jin
Jan 27, 2009·PLoS Biology·Arthur D LanderAnne L Calof
Mar 19, 2009·Mathematical Biosciences and Engineering : MBE·Wing-Cheong LoQing Nie
Nov 6, 2009·Cancer Research·Heiko EnderlingPhilip Hahnfeldt
Jul 30, 2010·PloS One·Craig J Thalhauser, Natalia L Komarova
Nov 18, 2010·Biophysical Journal·Ching-Shan ChouQing Nie
Nov 26, 2010·Nature·Rong WangViviane Tabar
Feb 5, 2011·Proceedings of the National Academy of Sciences of the United States of America·Gennady BocharovZvi Grossman
Mar 10, 2011·Nature Medicine·Hans Clevers
Jun 15, 2011·Cell·Benjamin D Simons, Hans Clevers
Nov 16, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ignacio A Rodriguez-BrenesDominik Wodarz
Dec 7, 2011·PLoS Computational Biology·Benjamin WernerArne Traulsen
Aug 10, 2012·Journal of Biological Dynamics·Yukihiko NakataTomás Alarcón
Apr 19, 2013·Frontiers in Oncology·Ignacio A Rodriguez-BrenesNatalia L Komarova
Jun 7, 2013·Journal of the Royal Society, Interface·Benjamin WernerArne Traulsen
Jul 3, 2013·Trends in Ecology & Evolution·Ignacio A Rodriguez-BrenesDominik Wodarz
Jul 5, 2013·Journal of the Royal Society, Interface·Ignacio A Rodriguez-BrenesNatalia L Komarova

❮ Previous
Next ❯

Citations

Feb 2, 2016·PLoS Computational Biology·Ivana BozicMartin A Nowak
Jan 20, 2018·PLoS Computational Biology·Fereshteh NazariTrachette L Jackson
Feb 27, 2017·Cancer Research·Ignacio A Rodriguez-BrenesDominik Wodarz

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alagille Syndrome

Alagille syndrome is a multi-system genetic disorder that can affect the liver, heart, and other parts of the body. It’s characterization includes heart problems, liver damage, jaundice, and xanthomas. Here is the latest research.

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Ignacio A Rodriguez-BrenesDominik Wodarz
Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Youfang CaoQing Nie
Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Youfang CaoJie Liang
© 2021 Meta ULC. All rights reserved