Identifying an ovarian cancer cell hierarchy regulated by bone morphogenetic protein 2

摘要: Whether human cancer follows a hierarchical or stochastic model of differentiation is controversial. Furthermore, the factors that regulate stem-like cell (CSC) potential are largely unknown. We used novel microfluidic single-cell culture method to directly observe capacity four heterogeneous ovarian populations defined by expression CSC markers aldehyde dehydrogenase (ALDH) and CD133. evaluated 3,692 progeny from 2,833 cells. found only ALDH(+)CD133(+) cells could generate all ALDH(+/-)CD133(+/-) identified clear branched hierarchy. also observed single putative event. Within hierarchy cells, bone morphologenetic protein 2 (BMP2) preferentially expressed in ALDH(-)CD133(-) BMP2 promotes expansion while suppressing proliferation As such, suppressed bulk growth vitro but increased tumor initiation rates, growth, chemotherapy resistance vivo whereas knockdown reduced numbers, chemoresistance. These data suggest pattern which acts as feedback mechanism promoting progenitor proliferation. results explain why suppresses vivo. Together, our support therapeutic target cancer.