Bidirectional interconvertibility between CSCs and non-CSCs?

Cancer stem cells: mirage or reality? Piyush B Gupta, Christine L Chaffer and Robert A Weinberg, Nat Med 2009(Sep); 15(9): 1010-1012 [Epub 2009(Sep 4)]. [FriendFeed entry] PubMed Abstract:

The similarities and differences between normal tissue stem cells and cancer stem cells (CSCs) have been the source of much contention, with some recent studies calling into question the very existence of CSCs. An examination of the literature indicates, however, that the CSC model rests on firm experimental foundations and that differences in the observed frequencies of CSCs within tumors reflect the various cancer types and hosts used to assay these cells. Studies of stem cells and the differentiation program termed the epithelial-mesenchymal transition (EMT) point to the possible existence of plasticity between stem cells and their more differentiated derivatives. If present, such plasticity would have major implications for the CSC model and for future therapeutic approaches.

Excerpt from the full text:

Figure 1: Stem-differentiation hierarchy.

[Figure]

Increased plasticity may be present within cancer populations, enabling bidirectional interconvertibility between CSCs and non-CSCs.

Last two sentences of the full text:

However, if non-CSCs can indeed give rise to CSCs, this plasticity would frustrate attempts to cure tumors by eliminating CSCs alone, as therapeutic elimination of CSCs may be followed by their regeneration from residual non-CSCs, allowing tumor regrowth and clinical relapse. We, therefore, suspect that optimal therapeutic regimens will need to incorporate agents that target both CSCs and non-CSCs if truly curative therapies are ever to be achieved.

Comment: This article presents a novel model of the "stem-differentiation hierarchy" involving CSCs and non-CSCs. The model includes the possibility that "a dynamic equilibrium may exist between CSCs and non-CSCs within tumors" that "may be shifted in one direction or another by contextual signals within the tumor microenvironment that influence the probability of interconversion between the CSC and non-CSC compartments ...". It's unfortunate that the article isn't openly accessible. If it were OA (with an appropriate Creative Commons License), a copy of the model depicted in Figure 1 could have been included in this post.

Gene signatures in residual breast cancers after conventional therapy

Gene Signature of Breast Cancer Stem Cells Revealed, Genetic Engineering & Biotechnology News, August 4, 2009. First paragraph:

A consortium of researchers have identified the gene expression patterns of breast cancer stem cells that remain post treatment with either chemotherapy or antihormone treatments. They report that this gene signature differs from those linked to the bulk of epithelial cells in the tumor.

Based on: Gene signature for cancer stem cells may provide drug targets, Glenna Picton, News Release, Baylor College of Medicine, August 4, 2009.

See also: Gene signature for cancer stem cells may provide drug targets, Science Centric, August 4, 2009. First paragraph:

A subset of tumour cells that remain after a woman with breast cancer undergoes treatment with either anti-cancer or anti-hormone therapy shows a 'gene signature' that could be used to define targets for developing new drugs against the disease, said a consortium of researchers led by Baylor College of Medicine. The report appears in the current issue of the Proceedings of the National Academy of Sciences.

The report referred to in the above excerpt is an Open Access publication: Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features by Chad J Creighton and 22 co-authors, including Michael T Lewis, Jeffrey M Rosen and Jenny C Chang, Proc Natl Acad Sci USA 2009(Aug 3). [Epub ahead of print].[Abstract][Early version of OA full text].

Cancer stem cells, hypoxia and metastasis

Cancer stem cells, hypoxia and metastasis, Richard P Hill, Delphine T Marie-Egyptienne, David W Hedley, Semin Radiat Oncol 2009(Apr);19(2):106-11. Abstract:

The successful growth of a metastasis, by definition, requires the presence of at least 1 cancer stem cell. Metastasis is a complex process, and an important contributor to this process is the influence of the tissue microenvironment, both cell-cell and cell-matrix interactions and the pathophysiologic conditions in tumors, such as hypoxia. A number of studies have suggested that normal stem cells may reside in “niches,” where cell-cell and cell-matrix interactions can provide critical signals to support and maintain the undifferentiated phenotype of the stem cells. In this article, the evidence that these niches may be hypoxic is described, and the potential role that hypoxia may play in maintaining the stem cell phenotype in cancers is discussed. Recent work has suggested that there may be a linkage between the stem cell phenotype and that induced by the process of epithelial-mesenchymal transition (EMT). EMT plays an important role in cell movement and organ formation during embryogenesis, and it is currently hypothesized to be a major mechanism by which epithelial cancers may generate cells that can form metastases. Recent evidence suggests that the expression of certain genes involved in EMT is influenced by low oxygen levels, again suggesting a linkage between stem cells and hypoxia. Whether this supposition is correct remains an open question that will only be answered by further experimentation, but the potential role of hypoxia is critical because of its widespread existence in tumors and its known role in resistance to both radiation and drug treatment.