[Background] The Musashi-1 (Msi-1) protein is a neural RNA-binding protein which is a marker of stem cells in nervous system. Msi-1 is also reported to be expressed in the crypt base columnar cells of mouse small intestine as well as in the nervous system, suggesting that Msi-1 will be a selective marker for stem cells also in gastrointestinal system. In 2004 AACR meeting, we demonstrated distribution of Msi-1 positive cells in human stomach. [Our findings in 2004] Msi-1 expression was observed predominantly in the epithelial cells of the isthmus/neck region in human stomach, while the epithelial cells in the upper part of the pit and in the base region of the glands were completely Msi-1 negative. Msi-1-positive cells were confirmed to be in a dormant state by PCNA/Ki-67 staining. In carcinogenesis, moderately Msi-1-positive cells were scattered in atypical gastric gland, stained in cytoplasm without localization as seen in normal gland. Msi staining level was weakened in early well differentiated adenocarcinoma, and disappeared in early poorly differentiated adenocarcinoma and advanced cancer. [Purpose] We are to investigate the Msi-1 expression in gastric cancer cell lines by immunocytochemistry, in order to suggest a hypothesis according to cancer stem cells using in vitro system. [Materials and Methods] Three kinds of human gastric cancer cells, TMK-1, MKN-45 and MKN74 are studied. Immunocytochemistry was performed for Msi-1, PCNA, cyclin D1, or beta-catenin. Cell proliferation assay is performed with cell count or MTT method. The concentration of cisplatin (CDDP) was each IC50 value of each cell line. [Results] No Msi-1 expression was observed in any proliferating cells in the three cell lines. After incubation with IC50 of CDDP, the rested survival cells showed Msi-1 positive staining, with specific localization in cytoplasm or nuclear. Approximately at 10-20 days after this, the cell starts to divide to proliferation with disappearing Msi-1 protein. In addition, characteristic analysis of the Msi-1 positive cells showed resistance to CDDP (wild type cell: Msi-1 positive cell =2.4:21.3 ug/ml in IC50 for CDDP), and no expressions of PCNA, cyclin D1, and beta-catenin, while wild type cell showed PCNA, cyclin D1 and beta-catenin expression without Msi-1 expression. [Conclusion] Although our findings will not be enough to suggest cancer stem cell system, it will be useful considering these findings to hypothesize that proliferating or differentiated cancer cells might own ability to alter themselves to be dormant (=cancer stem cells?).
[Proc Amer Assoc Cancer Res, Volume 46, 2005]