In the scientific literature of the last few years, various research groups have reported on their observations that the transition of epithelial cells to a mesenchymal (EMT) is a hallmark for the early stages of cancers. This EMT phase of neoplastic tissues is based upon the expression profile of a cell expressing an intermediate filament protein, vimentin, which is found in mesenchymal cells, but not in terminally differentiated epithelial cells. Vimentin is also found in many different neoplasms, particularly, those of mesenchymal cell origin that give rise to various forms of sarcomas. V. Vasko et al. from the Comprehensive Cancer Center at Ohio State University analyzed gene expression profiles of tumors from seven patients with highly invasive form of papillary thyroid carcinomas (PTCs). The investigators published their results in the February 20th issue of PNAS. With gene chip microarrays, the researchers found that the PTCs over-expressed TGF-β, NFκB, members of the integrin pathway, regulators of small G proteins, and CD42. It was also found that mRNAs encoding proteins involved in cell adhesion were expressed in reduced levels concomitant with over-expression of vimentin...a hallmark of EMT. Over-expression of vimentin was associated with PTC invasion and infiltration into the lymph nodes. In vitro studies, confirmed the functional role of vimentin in the development and maintenance of mesenchymal morphology as well as determining the invasive phenotype of the cancer in these thyroid tumors. (However, it is also known that vimentin along with desmin is expressed during early cellular development. The observations by Vasko et al. and other research groups raise the question whether EMT really occurs in these tumors. Is it possible that a subpopulation of primordial stem cells in these tumors, which are not contact inhibited and also expressing vimentin, may have become dysregulated and give rise to a "mesenchymal-like phenotype" in these papillary thyroid carcincomas? Further, would less differentiated cancer stem cells with high levels of vimentin give rise to a more invasive phenotype?)

As a follow-up to our January 25th post, we note that C. Li et al. also from the University of Michigan Medical Center published their study in the February 1st issue of Cancer Research on identifying cancer stem cells in pancreatic adenocarcinomas. The investgators identified a highly tumorigenic subpopulation (0.2 to 0.8% of total pancreatic cancer cells) of cancer cells in pancreatic cancers that were CD25+CD44+ESA+ (epithelial-specific antigen) - similar to the cancer stem cells found in head and neck cancers. These tumor cells had the capacity to self-renew and give rise to differentiated progeny cells. It was also found that these rare cancer stem cells expressed the developmental signaling molecule, sonic hedgehog (Shh). With immuno-compromised mice and tissue samples from 10 pancreatic cancer patients (8 primary and 2 metastatic), the researchers found that only 100 of the cancer stem cells expressing the above surface markers were needed to form a tumor in a mouse. Using flow cytometry to purify this subpopulation of stem cells, systemic injection of the cancer stem cells into the tail veins resulted in 50% of the mice having tumors. The xenografts histologically reflected the original human pancreatic tumors. Additionally, in a dose response experiment, it was found that at least 10,000 of the unsorted cancer cells were needed to form a tumor in a SCID mouse. (It is very interesting to note that more experimental data are demonstrating that various forms of cancers have a similar etiology, i.e. a cancer stem cell of the above phenotype that is highly tumorigenic.)