CD133 is a marker of gland-forming cells in gastric tumors and Sox17 is involved in its regulation

CD133 is a universal marker of tissue stem/progenitor cells as well as cancer stem cells, but its physiological significance remains to be elucidated. Here we examined the relationship between expression of CD133 and features of gastric epithelial cells, and found that CD133-positive (CD133[+]) tumor cell lines formed well-differentiated tumors while CD133-negative (CD133[-]) lines formed poorly differentiated ones when subcutaneously injected into nude mice. We also found that CD133(+) and CD133(-) cell populations co-existed in some cell lines. FACS analysis showed that CD133(+) cells were mother cells because CD133(+) cells formed both CD133(+) and CD133(-) cells, but CD133(-) cells did not form CD133(+) cells. In these cell lines, CD133(+) cells formed well-differentiated tumors while CD133(-) cells formed poorly differentiated ones. In human gastric cancers, CD133 was exclusively expressed on the luminal surface membrane of gland-forming cells, and it was never found on poorly differentiated diffuse-type cells. Considering that poorly differentiated tumors often develop from well-differentiated tumors during tumor progression, these results suggest that loss of expression of CD133 might be related to gastric tumor progression. Microarray analysis showed that CD133(+) cells specifically expressed Sox17, a tumor suppressor in gastric carcinogenesis. Forced expression of SOX17 induced expression of CD133 in CD133(-) cells, and reduction of SOX17 caused by siRNA in CD133(+) cells induced a reduction in the level of CD133. These results indicate that Sox17 might be a key transcription factor controlling CD133 expression, and that it might also play a role in the control of gastric tumor progression. (Cancer Sci 2011; 102: 1313-1321)