Fibroblasts induced epithelial to mesenchymal transition of tumor cells and their extra circulation traveling behavior

It is believed that tumor cells can detach from primary tumor site and disseminate in the circulation and tissues. These disseminated tumor cells can reside in the tissues for a long period that do not form the tumor mass, however, the potential of metastasis still remains. It is pivotal to tumor diagnosis and therapy to explore how these tumor cells behave after departing from the primary site. Once detached from the maternal site, the tumor cells firstly enter into the circulation and then into the tissues surrounded by the stromal cells, which may influence the tumor behaviors. In our previous study, we found that the normal fibroblasts were capable of inducting the epithelial into mesenchymal cells of the gastric tumor cells by the down regulation of the E-cadherin. The transformed gastric cancer cells exhibited impaired tumor colonization but increased metastasis, providing the preliminary cues for the fact that the transformed tumor cells exist in not only the circulation, but the tissue as well. Emerging studies have been focused on the biological behaviors of tumor cells in the circulation, while it is still not clear about of those cells out of circulation, especially in the early stage of cancer. In this article, we propose a hypothesis of the “traveling tumor cells” to include these tumor cells in the tissues based on our previous findings, which describe the tumor cells that migrate through the tissue with no evidence of tumor metastasis. Furthermore, we discuss the generation and underlying mechanisms of the “traveling tumor cells”, which we believe that they would be of great value to refresh our understanding of tumor metastasis.