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Titolo:
Bone marrow-derived cells contribute to tumor neovasculature and, when modified to express an angiogenesis inhibitor, can restrict tumor growth in mice
Autore:
Davidoff, AM; Ng, CYC; Brown, P; Leary, MA; Spurbeck, WW; Zhou, JF; Horwitz, E; Vanin, EF; Nienhuis, AW;
Indirizzi:
St Jude Childrens Hosp, Dept Surg, Memphis, TN 38105 USA St Jude ChildrensHosp Memphis TN USA 38105 t Surg, Memphis, TN 38105 USA St Jude Childrens Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA St Jude Childrens Hosp Memphis TN USA 38105 Oncol, Memphis, TN 38105 USA Univ Tennessee, Coll Med, Dept Surg, Memphis, TN 38105 USA Univ TennesseeMemphis TN USA 38105 Med, Dept Surg, Memphis, TN 38105 USA
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 9, volume: 7, anno: 2001,
pagine: 2870 - 2879
SICI:
1078-0432(200109)7:9<2870:BMCCTT>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
ENDOTHELIAL PROGENITOR CELLS; ANTIANGIOGENIC GENE-THERAPY; BLOOD-VESSEL FORMATION; IN-VIVO; NEOVASCULARIZATION; STRATEGIES; ORIGIN; CANCER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Davidoff, AM St Jude Childrens Hosp, Dept Surg, 332 N Lauderdale St, Memphis, TN 38105 USA St Jude Childrens Hosp 332 N Lauderdale St Memphis TN USA 38105
Citazione:
A.M. Davidoff et al., "Bone marrow-derived cells contribute to tumor neovasculature and, when modified to express an angiogenesis inhibitor, can restrict tumor growth in mice", CLIN CANC R, 7(9), 2001, pp. 2870-2879

Abstract

Inhibition of tumor-induced neovascularization appears to be an effective anticancer approach, although long-term angiogenesis inhibition may be required. An alternative to chronic drug administration is a gene therapy-mediated approach in which long-term in vivo protein expression is established. We have tested this approach by modifying murine bone marrow-derived cells with a gene encoding an angiogenesis inhibitor: a soluble, truncated form of the vascular endothelial growth factor receptor-2, fetal liver kinase-1 (Flk-1). Murine bone marrow cells were transduced with a retroviral vector encoding either truncated, soluble Flk-1 (tsFIk-1) together with green fluorescent protein (GFP) or GFP alone. Tumor growth in mice challenged 3 monthsafter transplantation with tsFIk-1-expressing bone marrow cells was significantly inhibited when compared with tumor growth in control-transplanted mice. Immunohistochemical analysis of tumors in each group demonstrated colocalization of GFP expression in cells staining with endothelial cell markers, suggesting that the endothelial cells of the tumor-induced neovasculature were derived, at least in part, from bone marrow precursors. These results suggest that long-term expression of a functional angiogenesis inhibitor can be generated through gene-modified, bone marrow-derived stem cells, andthat this approach can have significant anticancer efficacy. Modifying these cells seems to have the added potential benefit of targeting transgene expression to the tumor neovasculature, because bone marrow-derived endothelial cell precursors seem to be recruited in the process of tumor-induced angiogenesis.

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Documento generato il 01/12/20 alle ore 12:47:42