By Suling Liu, Hasan Korkaya, and Max S. Wicha | April 1, 2012
Inthe 30-year battle waged since the initiation of the war on cancer, there have been substantial victories, with cures for childhood malignancies among the most important. Our ever-expanding understanding of cellular and molecular biology has provided substantial insights into the molecular underpinnings of the spectrum of diseases we call cancer. Yet, while researchers view this as tremendous progress, many patients have seen only limited improvement. In fact, the relatively modest gains achieved in treating the most common malignancies have caused some to say that we are actually losing the war on cancer.
Based on new intelligence, oncologists are making informed battle plans to attack a particularly pernicious enemythe cancer stem cell. Controversial though they are, cancer stem cells are an incredibly promising target. If treatment-resistant cancer, and the metastases that transplant the cancer throughout the body, could be attributed to the actions of a single cell type, it could explain many of the treatment failures and provide a novel way to attack the disease.
The idea that cancers are driven by cells with embryonic features is an old one. Many cancers regress to a less differentiated state, expressing proteins that are usually expressed only in the embryo or during early development. It is only in the past 20 years or so, however, that additional observations led to the hypothesis that these embryonic-like cells were a separate subpopulation that fueled tumor expansion, much the same way that stem cells churn out the cells that make up a particular organ.
A number of groups, including our own, have identified cancer stem cell markers enabling the isolation and characterization of these cells. In addition, the development of in vitro and mouse functional assays has led to a veritable explosion of research on cancer stem cells from both blood-derived malignancies and solid tumors., However, the limitations of these markers and assays have generated heated debate regarding which tumors follow a stem cell model, and which do not. New data from our lab and from others is helping to clarify some of these areas of debate with the goal of better understanding how these cells can be identified and characterized.
A cancer stem cell (CSC) is defined as a cell that has the ability to self-renew, dividing to give rise to another malignant stem cell, as well as to produce the phenotypically diverse, differentiated tumor cells that form the bulk of the tumor. Evidence for CSCs was first documented in leukemia, where it was clear that only a small subset of cancer cells was capable of perpetuating the cancer upon serial transplantation from one mouse to another. Extensive knowledge of normal blood stem cells facilitated our recognition and understanding of leukemia stem cells. Evidence for CSCs in solid tumors has been more controversial, because it is more technically challenging to divide a solid mass into individual cells without damage or alteration, and knowledge of the properties of normal-tissue stem cells in these organs is more limited. However, some of the areas of contention may be resolved by continuing research into the biology of these CSCs.
Relatively modest gains achieved in treating the most common malignancies have caused some to say that we are actually losing the war on cancer.
One of the points of confusion in CSC biology is the question of where these cells come from. Do they arise from normal stem cells that have become cancerous through mutation, or do they arise from partially differentiated tissue-progenitor cells that have acquired the ability to self-renew? Recent evidence suggests CSCs may arise from either source.
A second misconception is that the definition of CSCs precludes the possibility that cancers arise from sequential mutations that accumulate over many cell generations and are selected for through a Darwinian processthe so-called clonal evolution model. Some have proposed that the CSC model is a competing theory of carcinogenesis. In fact, both models may be correct. There is evidence that CSCs may also be genetically unstable, resulting in clonal evolution that generates several distinct CSC clones in a tumor.
While the identification of CSC markers and the development of in vitro and mouse models have led to important advances in the field, each of these markers and models has limitations that have fueled debate. Markers used to isolate cancer stem cells, such as CD44, CD24, CD133, aldehyde dehydrogenase (ALDH), and Hoechst dye exclusion, have proven useful for identifying these cell populations in tumor samples. However, expression of these markers is highly dependent on experimental conditions such as culture medium and oxygen concentration. Similarly, in vitro assays that rely on the ability to form spherical colonies in suspension can be useful, but are notoriously inaccurate. Since the definition of CSCs is ultimately an operational one, the most reliable assay for these cells has been their ability to initiate tumors when transplanted into mouse models. Because the immune system will reject any implanted foreign tissue, researchers have had to use immunosuppressed mice to test for human CSCs. In some tumor types, such as melanoma, the proportion of cells capable of initiating tumors is dependent on the degree of immunosuppression in the mouse models utilized. However, the more immunosuppressed mouse models may actually overestimate the true frequency of CSCs.
Read the original post:
Are Cancer Stem Cells Ready for Prime Time?
- Stem Cells In Human Trials - September 15th, 2011 [September 15th, 2011]
- NZ Stemcell Trials - Part One - September 15th, 2011 [September 15th, 2011]
- CIRM Major Facilities Speed Stem Cell Science and Create Jobs - September 15th, 2011 [September 15th, 2011]
- Geron's Embryonic Stem Cell Clinical Trial for Spinal Cord Injury - September 15th, 2011 [September 15th, 2011]
- Hans Keirstead - Stem Cell Research Human Clinical Trials - September 15th, 2011 [September 15th, 2011]
- Stem-Cell Human Trials - September 15th, 2011 [September 15th, 2011]
- Geron: FDA Clearance for Human Clinical Stem Cell Trials - September 15th, 2011 [September 15th, 2011]
- Eric Legrand Rutgers University shout out, Listen up! - September 20th, 2011 [September 20th, 2011]
- How to Mend a Broken Heart - September 20th, 2011 [September 20th, 2011]
- Human Embryonic Stem Cell History! - September 20th, 2011 [September 20th, 2011]
- Robert Lanza - ACT - Stem cells and organ cloning interview - September 20th, 2011 [September 20th, 2011]
- Toonari Post Health News: Europe's first clinical trial using human embryonic stem cells - September 23rd, 2011 [September 23rd, 2011]
- Diabetes: Spotlight on Stem Cell Research - Ed Baetge - September 23rd, 2011 [September 23rd, 2011]
- Talking Apes being created by Science | Planet of the Apes, here we come! - September 24th, 2011 [September 24th, 2011]
- Health news: Internet use, sleep, human stem cell research - September 24th, 2011 [September 24th, 2011]
- Geron - September 24th, 2011 [September 24th, 2011]
- Batten Disease: Spotlight on Stem Cell Research - A Father's Story - September 24th, 2011 [September 24th, 2011]
- The Frankenstein Syndrome Trailer - September 24th, 2011 [September 24th, 2011]
- Leukemia: Spotlight on Stem Cell Research - Patient Stories - September 24th, 2011 [September 24th, 2011]
- Geron Corp. Initiates First Human Study Of Embryonic Stem-Cell Therapy - September 24th, 2011 [September 24th, 2011]
- Cardiovascular Therapies: Spotlight on Stem Cell Research - Yung-Wei Chi - September 24th, 2011 [September 24th, 2011]
- Stemcells come alive: Fix Mouse with severed spine ABCnews - September 24th, 2011 [September 24th, 2011]
- StemCells Gains 5% on Neural Stem Cell Trial in Spinal Cord Injury - September 24th, 2011 [September 24th, 2011]
- Stem-Cell Research on Animals - September 24th, 2011 [September 24th, 2011]
- First hESC Therapy Clinical Trial - September 24th, 2011 [September 24th, 2011]
- Stem Cell Testing on Human Subjects [Officially] Begins • NBC Nightly News • October 11th, 2010 - September 24th, 2011 [September 24th, 2011]
- Leukemia: Spotlight on Stem Cell Research - Catriona Jamieson - September 24th, 2011 [September 24th, 2011]
- First stem cell trial begins - September 24th, 2011 [September 24th, 2011]
- Parkinson's Disease: Spotlight on Stem Cell Research - Arnold Kriegstein - September 24th, 2011 [September 24th, 2011]
- Becoming a Blood Stem Cell Donor - September 24th, 2011 [September 24th, 2011]
- Stem cells might be able to reverse the effects of a heart attack. - September 24th, 2011 [September 24th, 2011]
- Horse Stem Cell Video.mp4 - September 25th, 2011 [September 25th, 2011]
- Stem cell trials to begin - September 25th, 2011 [September 25th, 2011]
- Lou Gehrig's Disease (ALS): Progress and Promise in Stem Cell Research - September 25th, 2011 [September 25th, 2011]
- Hans Keirstead - September 25th, 2011 [September 25th, 2011]
- Stem Cell Quiz - September 25th, 2011 [September 25th, 2011]
- NZ Stemcell Trials - Part Two - September 25th, 2011 [September 25th, 2011]
- Drug Trials in a Dish - September 25th, 2011 [September 25th, 2011]
- Rise and Walk - September 25th, 2011 [September 25th, 2011]
- Catriona Jamieson: Therapies Based on Cancer Stem Cells - September 27th, 2011 [September 27th, 2011]
- Vatican lending hand in adult stem cell research - September 28th, 2011 [September 28th, 2011]
- Why STEM-Enhance? - September 28th, 2011 [September 28th, 2011]
- Genetic Underpinnings of Alopecia Areata - September 29th, 2011 [September 29th, 2011]
- Batten Disease: Spotlight on Stem Cell Research - Ann Tsukamoto - September 29th, 2011 [September 29th, 2011]
- stem cell trial for leading causes of blindness - October 9th, 2011 [October 9th, 2011]
- Forbes Discusses Stem Cell Research - Video - October 13th, 2011 [October 13th, 2011]
- Bruce Conklin: Drug screening with stem cells - Video - October 13th, 2011 [October 13th, 2011]
- Human Trials of Embryonic Stem Cell Treatment Beginning - Video - October 13th, 2011 [October 13th, 2011]
- Rise and Walk - Video - October 13th, 2011 [October 13th, 2011]
- Mesenchymal Stem Cell Trials - Video - October 14th, 2011 [October 14th, 2011]
- Spinal Cord Injury: Progress and Promise in Stem Cell Research - Video - October 14th, 2011 [October 14th, 2011]
- Better Drugs Through Stem Cells - Video - October 16th, 2011 [October 16th, 2011]
- Adult Stem Cells Used To Rebuild Heart Tissue / Video - Video - October 16th, 2011 [October 16th, 2011]
- GARY RABIN- ADVANCED CELL TECHNOLOGIES 2011 - Video - October 21st, 2011 [October 21st, 2011]
- Stem cell treatment on horse a success, vet says - Video - October 21st, 2011 [October 21st, 2011]
- MAJOR EMBRYONIC STEM CELL BREAKTHROUGHS - Video - October 22nd, 2011 [October 22nd, 2011]
- Batten Disease: Spotlight on Stem Cell Research - Stephen Huhn - Video - November 13th, 2011 [November 13th, 2011]
- Human Cloning has Begun | Playing God? - Video - November 15th, 2011 [November 15th, 2011]
- Diabetes: Advancing Stem Cell Therapies - 2011 CIRM Grantee Meeting - Video - November 15th, 2011 [November 15th, 2011]
- Brain Tumors: Advancing Stem Cell Therapies - 2011 CIRM Grantee Meeting - Video - November 15th, 2011 [November 15th, 2011]
- Double Blind Trial of Stem Cells for Heart Failure - Video - December 4th, 2011 [December 4th, 2011]
- Cardiac Stem Cell Therapy Clinical Trial - Video - December 4th, 2011 [December 4th, 2011]
- Glasgow Hospital Conducts First Stem Cell Trials on Stroke Patients - Video - December 4th, 2011 [December 4th, 2011]
- Dr Dietrich discusses the Geron stem cell trial to treat acute spinal cord injury - Video - December 4th, 2011 [December 4th, 2011]
- Stem Cell Research Today: Larry Goldstein - CIRM Science Writer's Seminar - Video - December 7th, 2011 [December 7th, 2011]
- Stem Cell Clinical Trial for Heart Failure: Eduardo Marban - CIRM Spotlight on Disease - Video - December 22nd, 2011 [December 22nd, 2011]
- Clinical trials and stem cells: what patients should consider - Video - January 2nd, 2012 [January 2nd, 2012]
- Spare Parts for Humans: Tissue Engineers Aim for Lab-Grown Limbs, Lungs and More - Video - January 4th, 2012 [January 4th, 2012]
- CIRM Grant Writing: RFA's - Where does your Project Fit? - Video - January 5th, 2012 [January 5th, 2012]
- Prometheus and I: building new body parts from stem cells (15 Nov 2011) - Video - January 5th, 2012 [January 5th, 2012]
- News Bulletin 18 November 2011 -- The Christian Institute - Video - January 5th, 2012 [January 5th, 2012]
- The Brain on Trial: How Neuroscience Challenges the Law as We Know It - Video - January 5th, 2012 [January 5th, 2012]
- The Human Genome and Individualized Medicine - David Valle, MD - Video - January 5th, 2012 [January 5th, 2012]
- 2010 Professional of Distinction - Discovery Awards - Video - January 23rd, 2012 [January 23rd, 2012]
- Research at The Nebraska Medical Center Biologics Production Facility - Video - January 24th, 2012 [January 24th, 2012]
- ACT Announces Aberdeen Royal Infirmary in Scotland as Additional Site for Phase 1/2 Clinical Trial Using hESC-Derived ... - January 30th, 2012 [January 30th, 2012]
- StemCells, Inc. Announces Publication of Preclinical Data Demonstrating Its Human Neural Stem Cells Preserve Vision - January 31st, 2012 [January 31st, 2012]
- $30 million donation from Boris family will help McMaster turn stem cell research into therapy - February 6th, 2012 [February 6th, 2012]
- Stem Cell Treatment For Blindness Shows Promise In Trials - February 7th, 2012 [February 7th, 2012]
- ACT Announces Third Patient with Stargardt’s Disease Treated in U.S. Clinical Trial with RPE Cells Derived from ... - February 13th, 2012 [February 13th, 2012]