Findings overturn current beliefs that cellular differentiation is a one way process.
Scientists claim fully differentiated basal-like epithelial cells in breast tissue can spontaneously convert back to a stem cell-like state. The White Institute for Biomedical Research team says the finding represents the first time that this type of cell behavior has been observed in mammals and flies in the face of current dogma stating that cellular differentiation is a one way process.
The ability to retro-convert into a stem cell-like state was also evident in the neoplastic counterparts of the mammary gland cells, which could have major implications for the development of cancer therapies designed to eliminate cancer stem cells (CSCs), the researchers suggest. The potential for differentiated cancer cells to revert back into a stem cell state means the tumor may actually be able to generate a limitless supply of cancer stem cells for propagating itself.
On the positive side, the findings hint at the potential to generate patient- and tissue-specific stem-like cells in vitro via spontaneous conversion of a patient’s own terminally differentiated epithelial cells without the need for any genetic alteration. Such stem-like cells could be important for regenerative therapies, they note. The Whitehead Institute team’s research is published in PNAS in a paper titled “Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state.”
The Whitehead Institute research started when Christine Chaffer, Ph.D., noticed that human mammary epithelial (HME) cell cultures in their normal mammary epithelial growth medium contained a small proportion of cells that grew as floating cells above the majority population of adherent cells. These population, termed HME–floating cells (HME-flopcs), were then collected and cultured separately, yielding fully viable and, this time, adherent cell populations.
One of the HEM-flopcs cell types in the culture displayed markers similar to mammary progenitor/stem cells. The researchers were subsequently able to verify that this stem cell-like population had arisen from differentiated cells, and showed these cells could spontaneously generate cancer stem-like cells in mice.
The authors admit that further research needs to be undertaken to determine the mechanism underlying the de novo generation of CSCs from non-CSCs in vivo. However, as Dr. Chaffer and her colleagues point out, “our results further emphasize the pathological implications of cellular plasticity in cancer development, progression, and recurrence.
“This plasticity can occur naturally, and it seems that the trigger may be a physiological mechanism for restoring a pool of stem cells. We believe that certain cells are more susceptible to such a trigger and therefore conversion from a differentiated to a stem-like state, and that this process occurs more frequently in cancerous cells.”