Skip to main content
SpringerLink
Log in
Book cover

New Challenges for Cancer Systems Biomedicine pp 191–204Cite as

Cell-Cell Interactions in Solid Tumors — the Role of Cancer Stem Cells

  • Chapter

Part of the book series: SIMAI Springer Series ((SEMA SIMAI))

Abstract

It is increasingly argued that solid tumors follow a cellular hierarchy comparable to normal tissues, with so-called cancer stem cells on top of the hierarchy. In this model, cancer stem cells have the unique capability to initiate and propagate solid tumors. Non-stem cancer cells will form the bulk of the tumor population, but are by themselves incapable of giving rise to a continuously growing tumor. The two distinct phenotypes interact with one another and compete for common resources such as oxygen, nutrients, or available space. Single cell kinetics are parameterized with in vitro data and the interplay between cancer stem cells and their non-stem cancer cell counterpart is studied using two different modeling approaches: a cellular automaton model and a cellular Potts model. Simulations of tumor growth with both techniques reveal that cancer stem cell-driven solid tumors grow as conglomerates of self-metastases, suggesting a robust biological phenomenon. The growth rate of the tumor is dependent on the complex interplay of the underlying model parameters.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Al-Hajj, M., Wicha, M.S., Benito-Hernandez, A., Morrison, S.J., Clarke, M.F.: Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. USA 100, 3983–3988 (2003)

    Article  Google Scholar 

  2. Alarcón, T., Byrne, H.M., Maini, P.K.: A cellular automaton model for tumour growth in inhomogeneous environment. J. Theor. Biol. 225, 257–274 (2003)

    Article  MathSciNet  Google Scholar 

  3. Almog, N., Ma, L., Raychowdhury, R., Schwager, C., Erber, R., Short, S., Hlatky, L., Vajkoczy, P., Huber, P.E., Folkman, J., Abdollahi, A.: Transcriptional switch of dormant tumors to fast-growing angiogenic phenotype. Cancer Res. 69, 836–844 (2009)

    Article  Google Scholar 

  4. Anderson, A.R.A.: A hybrid mathematical model of solid tumour invasion: the importance of cell adhesion. Math. Med. Biol. 22, 163–186 (2005)

    Article  MATH  Google Scholar 

  5. Basanta, D., Hatzikirou, H., Deutsch, A.: Studying the emergence of invasiveness in tumours using game theory. Eur. Phys. J. B 63, 393–397 (2008)

    Article  MATH  MathSciNet  Google Scholar 

  6. Cipra, B.: An introduction to the Ising model. Am. Math. Monthly 94, 937–959 (1987)

    Article  MathSciNet  Google Scholar 

  7. Dewri, R., Chakraborti, N.: (2005) Simulating recrystallization through cellular automata and genetic algorithms. Modelling Simul. Mater. Sci. Eng. 13, 173–183

    Article  Google Scholar 

  8. Dingli, D., Michor, F.: Successful therapy must eradicate cancer stem cells. Stem Cells 24, 2603–2610 (2006)

    Article  Google Scholar 

  9. Dionysiou, D.D., Stamatakos, G.S., Uzunoglu, N.K., Nikita, K.S., Marioli, A.: A fourdimensional simulation model of tumour response to radiotherapy in vivo: parametric validation considering radiosensitivity, genetic profile and fractionation. J. Theor. Biol. 230, 1–20 (2004)

    Article  Google Scholar 

  10. Dunn, G.P., Bruce, A.T., Ikeda, H., Old, L.J., Schreiber, R.D.: Cancer immunoediting: from immunosurveillance to tumor escape. Nat. Immunol. 3, 991–998 (2002)

    Article  Google Scholar 

  11. Dunn, G.P., Old, L.J., Schreiber, R.D.: The three Es of cancer immunoediting. Annu. Rev. Immunol. 22, 329–360 (2004)

    Article  Google Scholar 

  12. Enderling, H., Alexander, N.R., Clark, E.S., Branch, K.M., Estrada, L., Crooke, C., Jourquin, J., Lobdell, N., Zaman, M.H., Guelcher, S.A., Anderson, A.R., Weaver, A.M.: Dependence of invadopodia function on collagen fiber spacing and cross-linking: computational modeling and experimental evidence. Biophys. J. 95, 2203–2218 (2008)

    Article  Google Scholar 

  13. Enderling, H., Anderson, A.R., Chaplain, M.A., Beheshti, A., Hlatky, L., Hahnfeldt, P.: Paradoxical dependencies of tumor dormancy and progression on basic cell kinetics. Cancer Res. 69, 8814–8821 (2009)

    Article  Google Scholar 

  14. Enderling, H., Hahnfeldt, P.: Cancer stem cells in solid tumors: Is evading apoptosis a hallmark of cancer? Prog. Biophys. Mol. Biol. 106, 391–399 (2011)

    Article  Google Scholar 

  15. Enderling, H., Hahnfeldt, P., Hlatky, L., Almog, N.: Systems Biology of tumor dormancy: linking biology and mathematics on multiple scales to improve cancer therapy. Cancer Res. 71, 2172–2175 (2012)

    Article  Google Scholar 

  16. Enderling, H., Hlatky, L., Hahnfeldt, P.: Migration rules: tumours are conglomerates of selfmetastases. Br. J. Cancer 100, 1917–1925 (2009)

    Article  Google Scholar 

  17. Enderling, H., Hlatky, L., Hahnfeldt, P.: Tumor morphological evolution: directed migration and gain and loss of the self-metastatic phenotype. Biol. Direct 5, 23 (2010)

    Article  Google Scholar 

  18. Enderling, H., Park, D., Hlatky, L., Hahnfeldt, P.: The importance of spatial distribution of stemness and proliferation state in determining tumor radioresponse. Math. Model. Nat. Phenom. 4, 117–133 (2009)

    Article  MATH  MathSciNet  Google Scholar 

  19. Folkman, J.: Tumor angiogenesis: therapeutic implications. New Engl. J. Med. 285, 1182–1186 (1971)

    Article  Google Scholar 

  20. Ganguly, R., Puri, I.K.: Mathematical model for the cancer stem cell hypothesis. Cell Prolif. 39, 3–14 (2006)

    Article  Google Scholar 

  21. Gerlee, P., Anderson, A.R.A.: An evolutionary hybrid cellular automaton model of solid tumour growth. J. Theor. Biol. 246, 583–603 (2007)

    Article  MathSciNet  Google Scholar 

  22. Glazier, J., Balter, A.:Magnetization to morphogenesis: A brief history of the Glazier-Graner-Hogeweg model. In: Anderson, A.R.A., Chaplain, M.A.J., Rejniak, K.A. (eds) Single-Cell-Based Models in Biology and Medicine. Birkhauser, Basel (2007)

    Google Scholar 

  23. Graner, F., Glazier, J.: Simulation of biological cell sorting using a two-dimensional extended Potts model. Phys. Rev. Lett. 69, 2013–2016 (1992)

    Article  Google Scholar 

  24. Hahnfeldt, P., Panigrahy D, Folkman J, Hlatky L.: Tumor development under angiogenic signaling: a dynamical theory of tumor growth, treatment response, and postvascular dormancy. Cancer Res. 59, 4770–4775 (1999)

    Google Scholar 

  25. Hanahan, D., Weinberg, R.A.: The hallmarks of cancer. Cell 100, 57–70 (2000)

    Article  Google Scholar 

  26. Hanahan, D., Weinberg, R.A.: Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011)

    Article  Google Scholar 

  27. Hatzikirou, H., Basanta, D., Simon, M., Schaller, K., Deutsch, A.: “Go or Grow”: the key to the emergence of invasion in tumour progression? Math. Med. Biol. 29, 49–65 (2010)

    Article  MATH  MathSciNet  Google Scholar 

  28. Hegedüs, B., Czirók, A., Fazekas, I., B’abel, T., Madar’asz, E., Vicsek, T.: Locomotion and proliferation of glioblastoma cells in vitro: statistical evaluation of videomicroscopic observations. J. Neurosurg. 92, 428–434 (2000)

    Article  Google Scholar 

  29. Hermann, P.C., Bhaskar, S., Cioffi, M.,Heeschen, C.: Cancer stem cells in solid tumors. Semin. Cancer Biol. 20, 77–84 (2010)

    Article  Google Scholar 

  30. Leder, K., Holland, E.C., Michor, F.: The therapeutic implications of plasticity of the cancer stem cell phenotype. PLoS ONE 5, e14366 (2010)

    Article  Google Scholar 

  31. Marciniak-Czochra, A., Stiehl, T., Ho, A.D., Jaeger,W., Wagner, W.:Modeling of asymmetric cell division in hematopoietic stem cells–regulation of self-renewal is essential for efficient repopulation. Stem Cells Dev. 18 377–385 (2009)

    Article  Google Scholar 

  32. Marian, C.O., Wright, W.E., Shay, J.W.: The effects of telomerase inhibition on prostate tumor-initiating cells. Int. J. Cancer 127, 321–331 (2010)

    Google Scholar 

  33. Metropolis, N., Rosenbluth, A.W., Rosenbluth, M.N., Teller, A.H., Teller, E.: Equation of state calculations by fast computing machines. J. Chem. Phys. 21, 1087–1092 (1953) 204

    Google Scholar 

  34. Morton, C.I., Hlatky, L., Hahnfeldt, P., Enderling, H.: Non-stem cancer cell kinetics modulate solid tumor progression. Theor. Biol. Med. Model. 8, 48 (2011)

    Article  Google Scholar 

  35. Mukhopadhyay, R., Costes, S.V., Bazarov, A.V., Hines,W.C., Barcellos-Hoff, M.H., Yaswen, P.: Promotion of variant human mammary epithelial cell outgrowth by ionizing radiation: an agent-based model supported by in vitro studies. Breast Cancer Res. 12, R11 (2010)

    Article  Google Scholar 

  36. Nakada, M., Anderson, E.M., Demuth, T., Nakada, S., Reavie, L.B., Drake, K.L., Hoelzinger, D.B., Berens, M.E.: The phosphorylation of ephrin-B2 ligand promotes glioma cell migration and invasion. Int. J. Cancer 126 1155–1165 (2010)

    Google Scholar 

  37. Norton, L.: Conceptual and practical implications of breast tissue geometry: toward a more effective, less toxic therapy. The Oncologist 10, 370–381 (2005)

    Article  Google Scholar 

  38. Norton, L.: Cancer stem cells, self-seeding, and decremented exponential growth: theoretical and clinical implications. Breast Dis. 29, 27–36 (2008)

    Article  Google Scholar 

  39. Piotrowska, M.J., Angus, S.D.: A quantitative cellular automaton model of in vitro multicellular spheroid tumour growth. J. Theor. Biol. 258, 165–178 (2009)

    Article  Google Scholar 

  40. Prehn, R.T.: Immunomodulation of tumor growth. Am. J. Pathol. 77, 119–122 (1974)

    Google Scholar 

  41. Prehn, R.T.: The inhibition of tumor growth by tumor mass. Cancer Res. 51, 2–4 (1991)

    Google Scholar 

  42. Rejniak, K.A., Anderson, A.R.A.: A computational study of the development of epithelial acini: I. Sufficient conditions for the formation of a hollow structure. Bull. Math. Biol. 70, 677–712 (2008)

    MATH  Google Scholar 

  43. Reya, T., Morrison, S.J., Clarke, M.F., Weissman, I.L.: Stem cells, cancer, and cancer stem cells. Nature 414, 105–111 (2001)

    Article  Google Scholar 

  44. Rich, J.N.: Cancer stem cells in radiation resistance. Cancer Res. 67, 8980–8984 (2007)

    Article  Google Scholar 

  45. Sabari, J., Lax, D., Connors, D., Brotman, I., Mindrebo, E., Butler, C., Entersz, I., Jia, D., Foty, R.A.: Fibronectin matrix assembly suppresses dispersal of glioblastoma cells. PLoS ONE 6, e24810 (2011)

    Article  Google Scholar 

  46. Shay, J.W., Wright, W.E.: Telomeres and telomerase in normal and cancer stem cells. FEBS Lett. 584, 3819–3825 (2010)

    Article  Google Scholar 

  47. Solé, R.V., Rodriguez-Caso, C., Deisboeck, T.S., Saldaña, J.: Cancer stem cells as the engine of unstable tumor progression. J. Theor. Biol. 253, 629–637 (2008)

    Article  MathSciNet  Google Scholar 

  48. Tang, J., Enderling, H., Becker-Weimann, S., Pham, C., Polyzos, A., Chen, C.Y., Costes, S.V.: Phenotypic transition maps of 3D breast acini obtained by imaging-guided agent-based modeling. Integr. Biol. (Camb) 3, 408–421 (2011)

    Google Scholar 

  49. Vermeulen, P.B., van Laere, S.J., Dirix, L.Y.: Inflammatory breast carcinoma as a model of accelerated self-metastatic expansion by intravascular growth. Br. J. Cancer 101, 1028–1029, author reply 1030 (2009)

    Google Scholar 

  50. Visvader, J.E., Lindeman, G.J.: Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat. Rev. Cancer 8, 755–768 (2008)

    Article  Google Scholar 

  51. Wang, Z., Zhang, L., Sagotsky, J., Deisboeck, T.S.: Simulating non-small cell lung cancer with a multiscale agent-based model. Theor. Biol. Med. Model. 4, 50 (2007)

    Article  Google Scholar 

  52. Wicha, M.S., Liu, S., Dontu, G.: Cancer stem cells: an old idea–a paradigm shift. Cancer Res. 66, 1883–1890,discussion 1895–1896 (2006)

    Article  Google Scholar 

Download references

Acknowledgements

The authors wish to thank Alberto d’Onofrio, Paola Cerrai, and Alberto Gandolfi for inviting us to contribute to this book, and Philip Hahnfeldt and James Glazier for their contribution to the original development of the different models that are summarized in this chapter. This project was supported by the National Cancer Institute under Award Number U54CA149233 to L.H. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

Author information

Authors and Affiliations

  1. Center of Cancer Systems Biology, Tufts University School of Medicine, St. Elizabeth’s Medical Center, 736 Cambridge Street, 02135, Boston, MA, USA

    Xuefeng Gao, J. Tyson McDonald, Lynn Hlatky & Heiko Enderling

Authors
  1. Xuefeng Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Tyson McDonald
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lynn Hlatky
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Heiko Enderling
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Heiko Enderling .

Editor information

Editors and Affiliations

  1. Department of Experimental Oncology, European Institute of Oncology, Milan, Italy

    Alberto d’Onofrio

  2. Department of Mathematics, University of Pisa, Italy

    Paola Cerrai

  3. Istituto di Analisi dei Sistemi ed Informatica “A. Ruberti“ — CNR, Rome, Italy

    Alberto Gandolfi

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Italia

About this chapter

Cite this chapter

Gao, X., McDonald, J.T., Hlatky, L., Enderling, H. (2012). Cell-Cell Interactions in Solid Tumors — the Role of Cancer Stem Cells. In: d’Onofrio, A., Cerrai, P., Gandolfi, A. (eds) New Challenges for Cancer Systems Biomedicine. SIMAI Springer Series. Springer, Milano. https://doi.org/10.1007/978-88-470-2571-4_10

Download citation

Publish with us

Policies and ethics

Search

Navigation