During normal development, epithelial cells can morph into a mesenchymal state, travel to their destination, and then flip back into an epithelial form. Many recent in vitro and animal studies have suggested that this “epithelial-mesenchymal transition” (EMT) and the converse mesenchymal-epithelial transition (MET) play a crucial role in metastasis of solid tumors.
That theory has been questioned because it has proven difficult to detect signs of EMT in human cancers. However, 2 studies published in June provide supporting evidence by detecting EMT markers in human circulating tumor cells (CTC).
Duke University scientists collected CTCs expressing EpCAM, an epithelial marker, from 41 men with castration-resistant prostate cancer and 12 women with metastatic breast cancer. More than 80% of CTCs from the men expressed multiple epithelial proteins such as cytokeratin and E-cadherin; mesenchymal proteins including vimentin, N-cadherin, and O-cadherin; and the stem cell marker CD133. Similarly, more than 75% of CTCs from the women expressed cytokeratin as well as vimentin and N-cadherin [Mol Cancer Res 2011 Jun 10 (Epub ahead of print)].
The researchers hypothesize that cells showing such combined markers may be in transition between states and thus particularly adept at metastasis. “These measurements don't prove plasticity for these cells, but they do provide supporting evidence for EMT in human cancer,” says first author Andrew Armstrong. He and Mariano A. Garcia-Blanco co-led these studies, which will be followed up with analyses of metastatic tumors from the same patients.
Separately, researchers at the Hellenic Oncology Research Group in Athens studied the expression of two EMT markers, twist and vimentin, in cytokeratin-expressing CTCs of 25 metastatic and 25 early breast cancer patients. Among CTCs from patients with early disease, 77% expressed vimentin and 73% expressed twist; those figures rose to 100% for both markers in patients with metastatic disease.
“The high incidence of these cells in patients with metastatic disease compared to early stage breast cancer strongly supports the notion that EMT is involved in the metastatic potential of CTCs,” the scientists reported (Breast Cancer Res 2011;13:R59).
