Replies

Results

• Nicola McCarthy

  13 April 2007 | 09:02

  Hi Dinesh,

  Thanks for you interesting comments on cancer stem cells—this is certainly a hot area of cancer research. And, yes as you point out many research groups are currently involved in identifying cancer stem cells. The consensus in the field is very much that cell surface markers and genetic markers along with the ‘spheroid’ assays are indicators of ‘stem cell-like’ behaviour, but this must always be verified by in vivo data; i.e. low numbers of the stem cell-like cells can reproduce the tumour. For further discussion on this point please see the Review by Vescovi and colleagues in Nature Reviews Cancer, and the Stem Cell Glossary by Austin Smith, published last year in Nature

• Hyukjin Cha

  19 April 2007 | 14:17

  Hi. It is fascinating idea that cancer can derive from the stem cells. Deregulated stem cells due to accumulated mutation or something derive cancerous progenitor cells and develop tumor.
  I agree that it is possible scenario in vivo and believe many studies that identify cancer stem cells from tumor. But I happen to know some groups try to sort stem cell like cells from cancer cell lines such as MCF7 or even Hela. Honestly, I am little skeptical about this idea. Mostly, they sort cancer cells out based on the fact that stem cells express high ABC transporters that may avoid Hoetchst33342 staining, named as side population cells (SP cells). SP cells in cancer cell lines are mostly under 1% (0.2 to 1% out of whole population). Some papers show that these cells can be even differentiated somehow. I am very confused because I assume that cancer cell lines are mostly homogenous not heterogeneous. When they sort them out and regrow in tissue culture condition, strangely similar population of SP cells is found.

  What do you think? Do you think their approach finding stem like cells from cell lines is reasonable?

  Here are some references that you may look up.

  PNAS vol.101 no 3 pp781-786 Jan 2004

  Cancer Res 2007;67(8):3716-24

• Dinesh Kumar Singh

  25 April 2007 | 19:28

  I highly appreciate the input from other members contributing in the discussion.
  I had been following most of the papers in cancer stem cell.Though people use the SP for identifying stem cell or cancer stem cell population, recent data however seems to nullify the strategy.Some people take these “so called cancer stem cells” from culture and do xenograft to prove the concept in invivo model. The serious flaw in this system is that the cancer cells which survive in the host system is in no way the same as those having stem cell phenotype.People attribute this to the differentiation process of the “same cancer stem cell”, though it might be that the change in environment from “tissue culture” system to invivo system simple forces the cells to acquire non-stem cell markers.This is but obvious.Isn’t it?
  How can we then claim that cancer originates because of the cancer stem cells which has the capacity for differentiation?As I had mentioned earlier, the expression of a few proteins does not at all mean that the functionality of the cell type has been restored. I really what understand what should be the criteria for “defining” the cancer stem cell, if at all it exists.Any say?
  Thanks in advance,
  Dinesh

• Bersenev Alexey

  02 May 2007 | 03:22

  Thanks to Dinesh Kumar Singh for such interesting topic!
  I’d say that fact of existence of CSC already out of discussion in scientific community. Defenition and statement of American Association for Cancer Research about it you can read here -

  Clarke M., Dick J., Dirks P. et al. Cancer Stem Cells—Perspectives on Current Status and Future
  Directions: AACR Workshop on Cancer Stem Cells. Cancer Res. 2006; 66: 9339-44.
  http://cancerres.aacrjournals.org/cgi/content/full/66/19/9339
  Other question is – “how CSC appear?” still under big disscussion –
  majority of labs consider that CSC arised from abnormal adult tissue SC (such as hematopoietic, muscle, neuronal or skin…), other opinion CSC appear from mutated progenitors or more mature cells (so called de-differentiation) and other possible mechanisms is spontaneous fusion.

  more recent review about it -
  Dalerba P, Cho RW, Clarke MF. Cancer Stem Cells: Model and Concepts. Annu. Rev. Med. 2007;
  58:267-284
  http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.med.58.062105.204854

• Hugh Blackbourn

  04 May 2007 | 16:27

  For anyone planning to be at Bio2007 next week, Corie Lok has pointed out that there’s a session on “Cancer Stem Cells – Stem Cell Biology Meets Oncology” on at 11.00 on Monday. Could be interesting if you happen to be in Boston…

• Corie Lok

  07 May 2007 | 18:07

  I’m at the BIO conference here in Boston and attended a cancer stem cells session this morning. Even though there are still plenty of research questions about the biology of cancer stem cells (as seen in this discussion), two US biotech companies are nevertheless forging ahead with the development of drugs that target receptors on the surface of cancer stem cells, in solid tumors and hemotologic cancers.

  Oncomed Pharmaceuticals and Stemline Therapeutics gave presentations today. Oncomed says it hopes to have its lead monoclonal antibodies in clinical trials by 2008 and Stemline says its drug has already been tested in 25 people in phase I clinical trials. So like many biotech companies, these two aren’t waiting for all the science to be in before diving into drug development.

• Dinesh Kumar Singh

  08 May 2007 | 22:57

  Dear Corie,
  Thank you for your information.Do you recall (if you attended the cancer stem cell meeting) any information as to which receptors or molecules were those Biotech companies happened to target.To my understanding, it is a highly immature decision to go clinical trials even before we know what it is or how does is it different from other “normal stem cells”.i repeat, the mere acquisition/expression of some of the stem cell markers does not necessarily mean that they have originated from stem cells and should be targeted for therapy.The root of the weed needs to be destroyed and not the attractive or lucrative branches or leaves.This would simply impede the progress of cancer therapy rather than augmenting it.

• Corie Lok

  09 May 2007 | 13:41

  Stemline said it was targeting the interleukin-3 receptor. The guy from Oncomed didn’t mention the specific receptors, but you can look up the details of their technology in their publications, listed and linked to from here. They’re commercializing the work of Michael Clarke and Max Wicha of the University of Michigan. Hope that helps!

• Stephen Loughran

  15 May 2007 | 01:46

  Hi,

  Stem cells are functionally defined, as being able to self-renew and to produce progeny that are able to differentiate into at least one more mature cell type, therefore acquiring a different phenotype to the stem cell of origin (i.e. something has to branch from the stem).

  Cancer stem cells (CSCs) should share these functions—the gold standard for identifying them should be the ability to serially transplant a relatively small number of putative CSCs to produce a large number tumour cells that are phenotypically distinct from the transplanted CSCs. I think that any cell that can’t do this isn’t truly a CSC, and any cancer that does not have this differentiating property (however abnormal it is) should not be considered to be derived from CSCs.

  I agree with Dinesh, that identifying supposed stem cell marker or stem cell associated properties such as Hoescht efflux, or even embryoid body formation, provide insuffcient evidence to be able to claim that a stem cell population has been identified.

• Bersenev Alexey

  17 May 2007 | 18:02

  Stephen,
  that’s exactly what last reviews and statement of AACR says
  in complete agreement with you like any scientist who work with stem cells

Results