Epithelial malignancies arise from one transformed cell emerged in otherwise normal epithelial sheets. It had not been clear what kinds of interactions occur between normal and transformed epithelial cells at this initial phase of carcinogenesis. I have obtained significant achievements as to this issue, thanks to this grant as follows;

(1) A mouse model has been established by which the “cell competition (competitive interactions between normal and transformed cells) (Curr Biol.,2012)” can be observed in a real-time manner. It is possible to induce significantly few mosaic RasV12-transformed cells among otherwise normal colonic crypts in Vil-CreER;LSL-RasV12-IRES-eGFP mice by administrating low amounts of Tamoxifen.

(2) By combining this mouse and an Award-winning Crypt Organoid system (Dr.Sato et al), it is now possible to observe RasV12 (eGFP(+))-transformed cells induced in colonic crypts under a microscope.

(3) We observed that most of the RasV12-transformed cells in the colonic crypts could be excluded to their apical sides within 48 hrs of their inductions.

Taken together, we clarified that that the “cell competition system” is really working in our mammalians and it is strongly suggested that our epithelial sheets harbor a robust self-defense mechanism against initial tumorigenesis (unpublished data). It is highly warranted to develop anti-tumor and/or tumor-preventive drugs depending on this “cell competition system”.