SAN FRANCISCO, CA USA (UroToday.com) - Epithelial-mesenchymal transition (EMT) has been demonstrated for a variety of cancers and is thought to correlate with metastatic potential, particularly in breast cancer. Colin Dinney, MD presented some basic and translational research results from his lab regarding the process of bladder cancer metastasis as it relates to EMT.
They created a bladder cancer cell line containing a reporter which can be monitored, in real time, by the emission of light. These tumorigenic cells, when implanted in immunodeficient mice, will metastasize. During the process of metastasis, circulating tumor cells (CTCs) can be isolated from peripheral blood samples. Global gene expression analysis showed that CTCs had a mesenchymal signature, and that the TGF-β pathway seemed to be active. CTCs were frequently coated with platelets and platelets are known to secrete TGF-β. “Master regulator”-type transcription factors like SNAIL are known to regulate the process of EMT in other tumor types, and seems to regulate it in bladder cancer too. SNAIL is expressed in CTCs. If SNAIL expression is blocked in the primary tumor, no metastases develop, nor are CTCs detected, but if the block is released, metastases develop and CTCs are detected. Interestingly, SNAIL is not expressed in the metastases, and metastases have more of an epithelial expression signature. This suggests that SNAIL is required for the genesis of CTCs through an EMT, but that a mesenchymal-to-epithelial transition is necessary for the metastasis to develop.
They extended these findings to human tissues, and showed that SNAIL was specifically expressed in 5 of 6 tumors where definitive lymphovascular invasion was present, and it was not expressed in other parts of the tumor. Dr. Dinney hypothesized that SNAIL expression was regulated by an epigenetic (i.e., plastic) program. He concluded by hinting that targeting this regulatory pathway might be difficult because it is not currently druggable.
Highlights of a presentation by Colin Dinney, MD at the 2014 Genitourinary Cancers Symposium - January 30 - February 1, 2014 - San Francisco Marriott Marquis - San Francisco, California USA
The University of Texas M. D. Anderson Cancer Center, Houston, TX USA