Evidence is accumulating that solid tumors contain a rare phenotypically distinct population of cells, termed cancer stem cells (CSC), which give rise to and maintain the bulk of the tumor. These CSC are thought to be resistant to current chemotherapeutic strategies due to their intrinsic stemlike properties and thus may provide the principal driving force behind recurrent tumor growth. Given the high frequency of recurrent metastasis associated with human ovarian cancer, we sought to determine whether primary human ovarian tumors contain populations of cells with enhanced tumor-initiating capacity, a characteristic of CSC. Using an in vivo serial transplantation model, we show that primary uncultured human ovarian tumors can be reliably propagated in NOD/SCID mice, generating heterogeneous tumors that maintain the histological integrity of the parental tumor. The observed frequency of tumor engraftment suggests only certain subpopulations of ovarian tumor cells have the capacity to recapitulate tumor growth. Further profiling of human ovarian tumors for expression of candidate CSC surface markers indicated consistent expression of CD133. To determine whether CD133 expression could define a tumor-initiating cell population in primary human ovarian tumors, fluorescence-activated cell sorting (FACS) methods were employed. Injection of sorted CD133 1 and CD133 2 cell populations into NOD/SCID mice established that tumor-derived CD133 1 cells have an increased tumorigenic capacity and are capable of recapitulating the original heterogeneous tumor. Our data indicate that CD133 expression defines a NOD/SCID tumor initiating subpopulation of cells in human ovarian cancer that may be an important target for new chemotherapeutic strategies aimed at eliminating ovarian cancer.
Abstract. Matches between the bills of hummingbirds and the flowers they visit have been interpreted as examples of coadaptation and feeding specialization. Observations of birds feeding at flowers longer or shorter than their bills combined with a lack of experimental evidence for foraging trade-offs, however, fail to support these interpretations. We addressed these inconsistencies by considering a seldom-studied dimension of hummingbird-flower relationships, the shape of bills and flowers, through experiments on the Purple-throated Carib, Eulampis jugularis, and its major food plant, Heliconia, in the eastern Caribbean. Bills of male E. jugularis are considerably shorter and straighter than bills of females. We examined foraging performances and trade-offs during visits to natural heliconias and 34 artificial flowers of differing length and curvature. Supporting predictions based on matches between bill and flower morphology, handling times of females were significantly shorter than those of males at the long, curved flowers of a green morph of H. bihai. Contrary to predictions, handling times of males were not significantly shorter than handling times of females at the short flowers of H. caribaea. At artificial flowers, maximum extraction depths of females were significantly longer than maximum extraction depths of males at all curved flowers, but not at straight flowers. Handling times of females were significantly shorter than handling times of males at the longest artificial flowers for all curvatures, whereas handling times of males were significantly shorter at short, straight, artificial flowers, but only while hover-feeding without a perch. Within each sex, handling times were inversely related to bill length at long flowers for all shapes. Taken together, these performance trade-offs suggest that the long, curved bills of females are adapted for feeding from long, curved flowers, whereas the short bills of males are adapted for hover-feeding from short, straighter flowers. In addition, the finding that differences in feeding performance occur at the extremes of floral phenotypes suggests that the evolution of bill morphology may be driven by a small subset of the flowers visited by a hummingbird species.
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