Stem Cell Reviews and Reports

, Volume 7, Issue 2, pp 227–237 | Cite as

Seeing is Believing: Are Cancer Stem Cells the Loch Ness Monster of Tumor Biology?

  • Justin D. Lathia
  • Monica Venere
  • Mahendra S. Rao
  • Jeremy N. Rich


Tumors are complex systems with a diversity of cell phenotypes essential to tumor initiation and maintenance. With the heterogeneity present within the neoplastic compartment as its foundation, the cancer stem cell hypothesis posits that a fraction of tumor cells has the capacity to recapitulate the parental tumor upon transplantation. Over the last decade, the cancer stem cell hypothesis has gained support and shown to be relevant in many highly lethal solid tumors. However, the cancer stem cell hypothesis is not without its controversies and critics question the validity of this hypothesis based upon comparisons to normal somatic stem cells. Cancer stem cells may have direct therapeutic relevance due to resistance to current treatment paradigms, suggesting novel multimodal therapies targeting the cancer stem cells may improve patient outcomes. In this review, we will use the most common primary brain tumor, glioblastoma multiforme, as an example to illustrate why studying cancer stem cells holds great promise for more effective therapies to highly lethal tumors. In addition, we will discuss why the abilities of self-renewal and tumor propagation are the critical defining properties of cancer stem cells. Furthermore, we will examine recent progress in defining appropriate cell surface selection markers and mouse models which explore the potential cell(s) or origin for GBMs. What remains clear is that a population of cells is present in many tumors which are resistant to conventional therapies and must be considered in the design of the next generation of cancer treatments.


Brain tumor stem cell Review Cell of origin Cancer stem cell hypothesis 



We sincerely apologize to those whose work we were unable to discuss due to space limitations. We would like to thank members of the Rich lab for stimulating discussion and critical review of this manuscript. Work in the Rich laboratory is supported by the Childhood Brain Tumor Foundation, the Pediatric Brain Tumor Foundation of the United States, Accelerate Brain Cancer Cure, Alexander and Margaret Stewart Trust, Brain Tumor Society, Goldhirsh Foundation, Duke Comprehensive Cancer Center Stem Cell Initiative Grant, and NIH grants NS047409, NS054276, CA112958, and CA116659. J.N.R. is a Damon Runyon-Lilly Clinical Investigator supported by the Damon Runyon Cancer Research Foundation. M.V. is supported by an American Brain Tumor Association Basic Research Fellowship and a National Service Research Award (NINDS F32 NS058042). J.D.L. is supported by an American Brain Tumor Association Basic Research Fellowship (sponsored by the Joelle Syverson Fund) and a National Service Research Award (NCI F32 CA142159).

Conflict of Interest

Dr. Mahendra S. Rao is an employee of Invitrogen Corporation, co-founder of Q Therapeutics, and currently serves at its Chief Scientific Consultant.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Stem Cell Biology and Regenerative MedicineLerner Research Institute, Cleveland Clinic FoundationClevelandUSA
  2. 2.Invitrogen CorporationCarlsbadUSA
  3. 3.Department of Stem Cell Biology and Regenerative MedicineCleveland ClinicClevelandUSA

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