When i have checked the proliferation marker (Cyclin D1) in cancer stem cell (CSC) then its expression was higher. However when i have developed the in vivo tumor which is highly aggressive and re-checked the status of cyclin D1 in these total tumors lysate by western. Result showed that there were no change of cyclin D1 expression in CSC in contrast to non-CSC, irrespective of tumors volume.
What type of cancer stem cell you used? Did you see the changes in tumor volume.
How did you isolate the cancer stem cell population?
Hi,
Its melanoma CSC and it exhibits higher tumor volumes. I am isolating these CSC by flow sorting.
In these cases, and I don't have any Lab experience in Cancer Cells, I'd say that seed, the cancer cell, is the same, but the soil, the Petri dish or a living thing tissue, differs.
From immune interactions to the microenvironment changes induced by the tumor cells, that have different actions when the cells are isolated in a culture or inside a tissue, many issues could be addressed as research subject in your question, that may have many types of answers.
The in vitro growth is higher because there are no interactions with tumor stroma, normal cells etc.
In vivo conditions are more complex e.g, the presence of competitor cell populations or quorum sensing-like signals modify the growth conditions not only for cancer stem cells but the activity of many other cells will change.
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Principally I share the view with Joseph Molnar. In many ways CSCs should behave very much like tissue-/organ-specific SCs, persisting in their 'SC-niche' in a quiescent state unless getting activated. By isolating these cells the restrictions/control of the microenvironment (neighboring cells, stromal cells, extracellular matrix) are released. So, growth in culture has in many aspects much in common with wound response or tissue/organ repair including accelerated proliferation.
As Dirk Breitkreutz mentioned , the microenvironment of CSCs cell in vivo could contain competitors and the outcome depends on the comparison of least resourche requirement between CSCs and one of the existing cell populations Other opportunity is that the inoculated cells are not able to suppress the immune system consequently the stem cells are eliminated directly or by the induction of apoptosis. as an alternative killing or inhibiting the growth of the transplanted cancer stem cells.
(I) Thinking it all over, also in regard to Joseph Molnar's comment on possible roles of immune (or inflammatory) responses, I got a few questions in return. Are your CSCs of human or mouse origin? For grafting in your tumor models are you using in case of mouse cells syngeneic mice or (mouse, human cells) nude or SCID mice? In SCID mice a human immune system can be installed. (II) What your data from the tumor models (in vivo) are concerned, also when grafting CSCs the majority of the resulting tumor cell population, being 'aggressive' (highly proliferative, invasive, destructing normal tissue - I assume), should be non-CSCs by definition. So, it wouldn't be too surprising that in both cases the outcome is quite similar (maybe earlier onset and higher efficiency with CSCs). By the way was inocculation at orthotopic sites?
Hi,
Thank you all for your valuable suggestions
My CSCs is mouse origin and we are grafting into NOD/SCID mice at orthotopic site.
Poor cells prisoneers of plastic dishes do not behave "exactly" like what they would do in their own "natural" environment ... e.g. a tiger in a zoo does not behave "exactly" like in its habitat ...
You should have a "in-depth" reading of the attached articles.
Best regards
Robert
Dear Dr. Robert,
Thanks for attaching those great articles.
Best
Maryada
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