Read about distinguishing cancer stem cells (CSCs) from its non-CSC counterpart based on stem cell surface markers, such as CD44, CD24, and CD133, is ambiguous and questionable. Is aldehyde dehydrogenase expression in cancer cells the hallmark of cancer stem cells?
High expression of ALDH is only responsible for detoxification, so that the combination with CD44(high)/CD24(low) subpopulation should be identified. As to whether or not CD133 is really a cancer stem cell marker is controversial in some kinds of cancer cells.
Dear Yoshida, thanks for your reply. Is CD44(high)/CD24(low) applicable to identifying cancer stem cell subpopulation of all cancer cell types?
It depends. In the case of breast cancer stem cells, CD44 (high)/ CD24 (low)/ ALDH1 (high) subpopulation is the most suitable one to identify CSCs. In the contrast, gastric and colon cancer stem cells highly express Lgr5 as well as CD44 regardless of the expression level of CD24, which is why the subset of CD44(high)/CD24(low) is not likely appropriate.
Depends on the type of cancer. For breast cancer, ALDH by itself can "enrich" for cancer stem cells from breast cancer cell lines. In primary tissue you need more markers like Ep-CAM/CD49f..etc. You can see our publication if you like http://www.ncbi.nlm.nih.gov/pubmed/23768049
The most important thing to know is that most commonly used cancer stem cell markers will NOT isolate pure population of stem cells. They will only enrich for CSCs.
Dear Hazem, thanks for directing me to your paper. Though I haven't read it, I believe it was another great work facilitating the advancement of cancer stem cell research. I'm working with pancreatic adenocarcinoma cell lines. In addition to breast cancer that you might have worked with, do you have any idea of how well does ALDEFLUOR kit (Stemcell Technologies) enrich the pancreatic cancer stem cell subpopulation that is present within the pancreatic cancer cell lines?
Did you also mean that we are still far from defining the CSCs correctly by using the cancer stem cell markers that have been reported thus far?
With my limited knowledge in pancreatic cancer cells, CD133 is one of the best markers for CSCs. As for the second question, yes..all these markers do not identify purely CSCs, they just enrich for it.
This is not a straightforward question, nor is there a straightforward answer. With regards to ALDH1 vs CD133 identifying pancreatic CSCs, it is best to consult the body of literature available to determine which is best.
In comparing ALDH1 to cell surface phenotypes across cancer types, ALDH1 has been shown to enrich for stem cells in a broad range of normal and cancerous tissues. Conversely, many cell surface phenotypes are restricted to a specific cancer type. ALDH1 also plays a biological role in stem cells, whereas the cell surface markers typically have no known role in stem cell function or maintenance. This has lead some to propose that high ALDH1 activity is a universal property of stem cells.
Obviously, you need to consult the literature for any given cancer to be sure and validate your isolation method. However, in absence of any strong evidence to the contrary, I would trust in ALDH1 as a CSC marker more so than the cell surface phenotypes.
Dear Nick and Allison, thanks for the product recommendation and useful advice.
I agree with Hazem Ghebeh. The type of marker to identify CSCs varies depending on the type of cancer. Also, the markers only enriches the CSCs. It is never a 100 % pure CSCs that we isolate with any one of the available markers. What may work best is to use multiple markers to isolate a tight cluster very enriched CSCs. At the same time performing a few very basic assays to confirm CSCs with every possible isolations and having the right positive controls for the other experiment helps.
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