THE BACTERIAL COLICIN ACTIVE AGAINST TUMOR-CELLS IN-VITRO AND IN-VIVO IS VEROTOXIN-1

被引:79
作者
FARKASHIMSLEY, H
HILL, R
ROSEN, B
ARAB, S
LINGWOOD, CA
机构
[1] UNIV TORONTO,DEPT MICROBIOL,TORONTO,ON M5S 1A4,CANADA
[2] UNIV TORONTO,DEPT MED BIOPHYS,TORONTO,ON M5S 1A4,CANADA
[3] UNIV TORONTO,DEPT MED,TORONTO,ON M5S 1A4,CANADA
[4] UNIV TORONTO,DEPT CLIN BIOCHEM,TORONTO,ON M5S 1A4,CANADA
[5] UNIV TORONTO,DEPT BIOCHEM,TORONTO,ON M5S 1A4,CANADA
[6] PRINCESS MARGARET HOSP,ONTARIO CANC INST,TORONTO,ON M4X 1K9,CANADA
[7] TORONTO HOSP,DEPT GYNECOL & ONCOL,TORONTO,ON M5G 2C4,CANADA
[8] HOSP SICK CHILDREN,RES INST,DEPT MICROBIOL,TORONTO,ON M5G 1X8,CANADA
关键词
RECEPTOR GLYCOLIPID; GLOBOTRIAOSYL CERAMIDE; OVARIAN CANCER; FIBROSARCOMA; ANTIMETASTATIC;
D O I
10.1073/pnas.92.15.6996
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We have identified verotoxin 1 (VT1) as the active component within an antineoplastic bacteriocin preparation from Escherichia coli HSC10 studied over two decades, Recombinant VT1 can simulate the toxicity of anticancer proteins (ACP), and the antineoplastic activity of ACP (and VT1) was abrogated by treatment with anti-VT1 antibody, Similarly, VT1 mimics the protective effect of ACP in a murine metastatic fibrosarcoma model, Prior immunization with VT1 B subunit prevents the effect of VT1 or ACP in this model, The activity of ACP against a variety of human ovarian cell lines was mimicked by VT1, and multidrug-resistant variants were significantly hypersensitive, Primary ovarian tumors and metastases contain elevated levels of globotriaosylceramide compared with normal ovaries, and overlay of frozen tumor sections showed selective VT binding to tumor tissue and the lumen of invading blood vessels, Our contention that VT1 could pro,ide an additional approach to the management of certain human neoplasms is discussed.
引用
收藏
页码:6996 / 7000
页数:5
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