Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

Mesenchymal-transitioned epithelial cancer cells instigate EMT via paracrine WNT signal (#106)

Shinichiro Kato 1 , Satoru Yokoyama 1 , Yoshihiro Hayakawa 1 , Ikuo Saiki 1
  1. Pathogenic Biochemistry, Institute of Natural Medicine , University of Toyama, Toyama, Japan

Epithelial-to-mesenchymal transition (EMT) plays an important role in cancer cell malignancy and metastatic potential, and indeed epithelial and mesenchymal cancer cells are often heterogeneously interspersed in tumor invasive front. Although such intra-tumor heterogeneity may account for the malignant behavior of cancer cells, it is not known whether mesenchymal transitioned cancer cells (M-cells) can cross-talk with epithelial cancer cells (E-cells) within the heterogeneous tumor microenvironment. In this study, we tested the potential of M-cells to instigate EMT of surrounding cancer cells by using human epithelial Panc-1 or A549 cancer cells treated with TGF-β to induce EMT. In co-culture experiments of E- and M-cells in both cell lines, we have found that the conditioned medium (CM) of M-cells induced EMT in E-cells and further demonstrated WNT inhibitors, IWP-2 and rhDKK1, inhibited such M-cells induced EMT. The critical contribution of WNT pathway was confirmed by siWNT3 and siWNT5B transfection into M-cells. Furthermore, CM of M-cells also has unexpected role for induction of MET in M-cells itself. Importantly, the interaction between E- and M-cells could dynamically reinforce tumor in vivo metastatic potential. These results implicate that mesenchymal-transitioned cancer cells could control intratumoral EMT and also MET, and in particular, instigate EMT of surrounding cancer cells through paracrine WNT signal pathway including WNT3, to enhance metastatic spread to distant organs.