Stem Cell Alter Egos

Researchers show that cancer stem cells can exist in two distinct and interconvertible states.

By Abby Olena | April 1, 2014

TWO-FACED: The invasive edge of a tumor (left) harbors mesenchymal-like breast cancer stem cells (green), while the interior of the tumor (right) contains epithelial-like cancer stem cells (pink).REPRINTED FROM S. LIU ET AL., STEM CELL REPORTS, 2:78-91, 2014


The paper
S. Liu et al., “Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts,” Stem Cell Reports, 2:78-91, 2014.

The states
Cancer metastasis is thought to rely on tumor cells losing their polarity and their connections with neighbors, enabling them to migrate and invade other tissues—an epithelial-to-mesenchymal transition. The reverse process—the mesenchymal-to-epithelial transition—then allows cells to set up shop in a new tissue. Cancer stem cells can express genes associated with both pathways, but there have been conflicting findings about the relationship between stemness and these transitions.

The finding
Cancer biologist Max Wicha of the University of Michigan and colleagues showed that breast cancer stem cells (BCSCs) in the same tumor can exist in both states. They found invasive, mesenchymal-like BCSCs at the edges of tumors, while proliferative, epithelial-like BCSCs were localized toward tumors’ interiors. The researchers also demonstrated that the two states are interconvertible, and they suggested that this plasticity might be required for metastasis.

The resolution
“Heterogeneity of breast cancer stem cells . . . has been an area of intense investigation and, frankly, confusion for a lot of people,” says Charlotte Kuperwasser of Tufts University School of Medicine who was not involved in the work. By showing that BCSCs can alter their identity, the authors “have done a good job of unifying the field and observations that others have made,” she says.

The applications
Although breast cancer subtypes are treated differently in the clinic, “the stem cells have much more in common than we thought,” Wicha says. “As we develop therapies that can target cancer stem cells, they may be useful in [multiple] forms of breast cancer.”

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April 14, 2014



1. is the cellular diversity( epithelial, mesenchymal) noted within the cancer continuum/block  a metaplasia or a de novo divergent differentiation  from a common cellular anlage


2. what is the role of local vascularity in this diversity; eg blood supply per unit weight of cancer mass.


3. does diminished vascularisation favour mesenchymal morphogenesis over epithelialism


4 does diminished vascularisation reduce cohesiveness within the cancer block and thus easier disaggregability of cells with facilitation of embolisation/metastases


5. has any attention been paid to cell types in the interval between the central and the peripheral zones of the cancer with regards to architectural gradualism or abruptness within the cell types; in other words, is the change in cell type ( epithlium - mesenchymal) a phenotypic gradualism between the centre and the periphery or quantum leap from one cell type to another.

in clinical work, we do know that there tends to be increasing hypoxia the deeper into the cancer bulk one goes; an observation with significant therapeutic implications in radiation treatment as well as in surgerey regarding the amount of haemorhage to be anticipated in cancer dissection during surgery.

it is also believed that mesenchymal cells are less vulnerable to hypoxia than well differentiated epithelial cells and so the observation in this study might well be another indication of evolutionary adaptation by the cancer cells to survive the odds both in terms of success at the locus morbi and success further afield ( metastic destination).

there is then the clinical anxiety about the capability of mesenchymal cells, using their relative stemness, to diffentiate at the receiving end into biologically more aggresive variants of the original tumour with implications for the kind of therapy that needs be customised to such variant..

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