Dear colleagues,

If one believes that cancer originates from cancer stem cells or even if one believes cancer stem cells are the only cancer cells capable of self-renewal (key property), one can conclude that cancer stem cells don't always metastasize as not all patients develop metastases. As the sites of metastases also differ among cancer types, it is clear that the host tissue microenvironment affects the regional self-renewal of cancer stem cells or their progeny.

Do patients with metastases have a greater percentage of cells with stemness features ? Unknown

Can cancer cells gain stem cell properties in a tissue specific manner, such that the metastasizing cell becomes capable of self-renewal only after metastases ? Unknown but quite possible if one considers how quickly liver metastases grow when compared to bone metastases

Are cancer stem cells a unique population of cells or do they represent cancer cells that have acquired stemness properties at a given point in time either stochasticaly or under influence of tissue factors/cytokines etc: Unknown but plausible.

At this point in time, we have ,ore questions than answers.

I am no sure anyone has the answer your question yet. I worked with brain tumor and I can tell you from my experience in glioma. If you FACS sort CD133+glioma stem cells (GSCs), CD15+ GSC and unsorted tumor cells and implant theses subpopulations in the nude mice brain they behave completely differently. CD133+ GSC tumors are very invasive, CD15+ GSC tumors are extremely vascular and unsorted parental tumors are in between… so it is possible that post therapy if only cells survive is CD133+ GSC, than the tumor can become very invasive… and which is the case for the patients with glioma….but the data regarding the of the cells population post chemo and radiotherapy is not yet well characterized…

It is not necessarily the specific stem cell lineage responsible for metastasis. However, it has been documented that that preexisting clones of cells,possibly derived through clonal expansion and clonal selection, have selective advantage in vascular invasion and thereby tumor metastasis.

Thank you.

It is not necessary for cancer metastaisis that cancer stem cells exist. However, aggressive colonies is more often formed by cancer stem cells.

i guess that the stem cells have very less property of local adhesion. May be this less abundant property is helpful for cell migration during development. this makes them more likely to metastasize.

In contrast, the cells other than the above type may have comparatively more adhesive property that may lead to slow or late metastasis.

Dear Guruprasad, I think that what you are talking about is in vitro properties of stem cells during development, which in epithelial tumors in vivo don't seem to be existing. Secondly, if we take into consideration more well documented process i e EMT, then epithelial cell is one differentiated form and mesenchymal cell another differentiated form in the spectrum, and the process is responsible for invasability and possibly metastasis as per latest theory., again stem cells nowhere seem to be involved.Moreover as I said earlier, there are metastatic clones emerging through clonal evolution.

Dear colleagues,

If one believes that cancer originates from cancer stem cells or even if one believes cancer stem cells are the only cancer cells capable of self-renewal (key property), one can conclude that cancer stem cells don't always metastasize as not all patients develop metastases. As the sites of metastases also differ among cancer types, it is clear that the host tissue microenvironment affects the regional self-renewal of cancer stem cells or their progeny.

Do patients with metastases have a greater percentage of cells with stemness features ? Unknown

Can cancer cells gain stem cell properties in a tissue specific manner, such that the metastasizing cell becomes capable of self-renewal only after metastases ? Unknown but quite possible if one considers how quickly liver metastases grow when compared to bone metastases

Are cancer stem cells a unique population of cells or do they represent cancer cells that have acquired stemness properties at a given point in time either stochasticaly or under influence of tissue factors/cytokines etc: Unknown but plausible.

At this point in time, we have ,ore questions than answers.

We define CSC by their nature of self renewal, multipotency to yield variable lineages, difficulty to eradicate with drugs. We recognize CSC by their looks (f.i., CD34+). There is a gap, that may become a trap: not for the SC, but for us.

Possibly underestimated: CSC may be most capable to adapt to (the restrictions posed by) the micro-environment. From a recent study by J Oliveira (Glycobiology 2010, 20:1341) it became evident that properties (determined by expression of glycoproteins) of metastatic cells (including CSC?) changed from the primary site as compared to intra-vessel micrometastases. Furthermore, CSC may at times be dependent upon other cancer cells to accomplish distant growth. So let us take those versatile properties into account when assessing the role of CSC in their - for a host negative - behavior. And if you know you to accomplish that, gimme a ring.

I feel this question would need many full lines of research just to ascertain where to look at; an old Science-fiction tale spoke about somewhere in the universo, a computer stored all science, and was able to reply or solve any question. Some scientists asked it about several subjects, with no reply; after several silences, one asked the savant computer the reason why, when knowing everything, it didn't gave a reply, the solution to this question was "To make an appropriate question, you need knowing most of the answer". Many would like having found a reply to your question, that anyway does stimulate the people working in the field, I don't, as my field is clinic, not bench. Regards

It appears that cancer stem cells can be regarded as the spearhead of the cancer load, demonstrating more aggressive biological behavior and therefore it can be assumed that they can metastasize more easily and resist to (neo)adjuvant treatment at the metastatic sites. However, the development of metastatic sites also depends significantly on the characteristics of their local micro-environment. From this point of view, even non-stem cancer cells could be easily attracted to sites with increased local inflammation or impaired microvascular function, with one of the main mechanisms being for instance their adhesion to activated platelets. It is my belief that the metastatic disease is a balance between the biological aggressiveness of the cancer cells and the tissue susceptibility to host the metastatic nests. As a result, even a non-stem cancer cell can metastasize in areas of increased oxidative stress. Cancer is a systematic disease even when with the current diagnostic means we cannot detect it.

CSC are critical indeed to trigger metastasis - but when performing xenograft experiments, this is not the only issue - mice strain is as critical - a same cell line (e.g., MDA231 breast cancer cells) yields 0% of metastasis in NMRI mice, about 10% in swiss nu/nu, and 100% in NSG mice. It all depends of the remaining immune system in the animals, all other parameters being the same (matrigel-based engraftment of 100 000 cells, in our case). Back to CSC, it is acknowledged now that even clones from the ATCC have CSC - the proportion of which may vary, thus impacting on the invasiveness of the cell lines eventually. This is why the initial number of cells in the graft may plays a role - the bigger is the graft, the higher will be the number of CSC. In my lab, we do not go below 30 000 cells when working on the meta issue, and we use NSG mice only. I hope this helps!

This article may be or your interest:

Nature. 2011 Dec 7;481(7379):85-9. doi: 10.1038/nature10694.

Interactions between cancer stem cells and their niche govern metastatic colonization.

Malanchi I, Santamaria-Martínez A, Susanto E, Peng H, Lehr HA, Delaloye JF, Huelsken J.