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- W2977737059 abstract "3762 In its normal life cycle, B. pertussis attaches to, and invades ciliated epithelia and macrophages of the human airways, using adhesins specialized for certain oligosaccharides and proteins on these cells. Here we report that B. pertussis uses similar mechanisms for invasion of a variety of human cancer cells in vitro, and exhibits potent, invasion-dependent, cytotoxicity. In a 30′ in vitro invasion assay, B. pertussis invaded human SKmel-23 melanoma cells at 20-30 times the rate for normal human melanocytes and fibroblasts. B. pertussis invasion of SKmel-23 cells was inhibited by preincubation of cancer cells with glycosidase F, the plant lectins LPHA and TGP, human antibodies vs CD15 and CD11b, or the RGD tripeptide sequence—implying that the structural requirements for invasion included β1,6-branched N-glycans, Lewis × antigens, CD11b, and the sequence arg-gly-asp respectivelly. Invasion was also inhibited by preincubation of cancer cells with 3-methyladenine (3-MA), indicating a role for phagolysosomal vacuole formation in uptake of B. pertussis by the cancer cells. When fixed, paraffin-embedded sections of human cancers were re-hydrated, incubated with B. pertussis, and then stained with LPHA for β1,6-branched N-glycans, bacteria were seen attached specifically to the sugar-rich regions of the tumors. Exposure of human SKmel-23 melanoma, MCF-7 breast carcinoma, or A549 lung carcinoma cells in culture to Bordetella pertussis caused marked morphological changes and massive lysis of the cells. Lysis was largely prevented by simultaneous treatment with 3-MA. B. pertussis targeted A549 human lung carcinomas growing s.c. in nu/nu mice. Regarding tumor growth, in an on-going experiment with A549 tumors, in the 8 saline-injected control mice, each individual tumor increased in size over 77 days with a mean 15-fold increase in mass. In contrast, of the 16 bacteria-injected mice, each tumor eventually ceased growing or decreased in mass, such that at 77 days after initiation of treatment, the mean tumor size was unchanged from the starting size, with several cases of regression and scarring. Regarding safety, i.v.-injected B. pertussis showed no toxicity toward the mice after repeated injections of the highest dose of bacteria tested (5 × 108 cfu/mouse). Thus for a number of reasons, B. pertussis appears to be a promising new anticancer vector." @default.
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- W2977737059 date "2004-04-01" @default.
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- W2977737059 title "Bordetella pertussis exhibits specific attachment, invasion, and cytotoxic capabilities toward human cancer cells." @default.
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