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Coukos/Macmillan
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5 I8 V1 b3 x+ }, XDendritic cells present antigens during immune responses and are thought to be important in antitumor activity. However, under the influence of the known cancer promoter VEGF-A, dendritic cell precursors take on the trappings of endothelial cells and contribute to tumor blood vessels, speeding the cancer's growth, according to a report by Jose Conejo-Garcia, Fabian Benencia, George Coukos (University of Pennsylvania Medical Center, Philadelphia, PA), and colleagues.
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Hoping to boost anti-tumor immunity in a mouse model of ovarian cancer, Conejo-Garcia et al. found that expression of the inflammatory peptides ?-defensins attracted dendritic cells to the tumor. In tumors with low levels of VEGF-A, the immune cells slowed the cancer's growth presumably via anti-tumor immunity, but when VEGF-A was abundant, they actually promoted tumor growth via increased vascularization. The dendritic cells started expressing endothelial cell surface markers and were incorporated into the tumor vasculature.
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Previous work suggested that this type of dendritic cell conversion to an endothelial cell phenotype could occur in vitro, but this is the first report of it in vivo. To determine if the observation was an artifact of their mouse model or if it occurs in spontaneous human cancers, the team examined human tumor samples. ?-defensin is expressed in both ovarian neoplasias and healthy postmenopausal ovaries, but occurs at seven times higher levels in advanced rather than early stage cancers. Moreover, the team found a population of tumor-localized leukocytes that had cell surface markers indicative of dendritic cells and endothelial cells, similar to those cells in the mouse model. Finally, cancers with high levels of VEGF-A and ?-defensins had more vasculature than those with lower levels, suggesting that dendritic cells do convert to vascular cells in human cancers.$ w" \' M: X1 ?& T3 I
- N) W+ u; V9 K/ X( e3 S' Y"This is a totally new paradigm for dendritic cell biology," says Coukos. The team has looked primarily at ovarian cancers, but Coukos thinks the phenomenon is likely to be common in solid tumors. Whether or not there is a healthy reason for dendritic cells to participate in vasculogenesis is unclear.
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7 L% k8 X* z3 bConejo-Garcia, J.R., et al. 2004. Nat. Med. doi:10.1038/nm1097.(Dendritic precursor cells (brown) contri) |
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发表于 2009-3-6 08:28
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