Vascular gene transfer driven by endoglin and ICAM-2 endothelial-specific promoters

Velasco, Beatriz; Ramírez, José Ramón; Relloso, Miguel; Li, C.; Kumar, Shant; López‐Bote, Juan Pedro; Pérez‐Barriocanal, Fernando; Jm, López-Novoa; Cowan, Peter J.; D'apice, A. J. F.; Bernabeu, Carmelo

doi:10.1038/sj.gt.3301468

Cited by 39 publications

(23 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Retardation of tumor growth and reduced incidence of chemically induced skin papillomas in S-Eng þ transgenic mice Although blood vessel formation during embryonic development and in the vasculature of adult animals were apparently normal in S-Eng þ transgenic mice (Velasco et al, 2001), we analysed whether these mice showed an altered angiogenic tumor phenotype. To this aim, we compared the growth and vascularization of tumors induced in S-Eng þ and control mice upon s.c. injection of Lewis lung carcinoma (3LL) cells, a widely used in vivo model for tumor angiogenesis and metastatic infiltration (Portella et al, 2003).…”

Section: Transgenic Expression Of S-endoglin Does Not Rescue the Lethmentioning

confidence: 99%

“…To determine the effect of S-endoglin on the vascular-specific rescue of this lethal phenotype, we took advantage of a previously generated transgenic line of mice (S-Eng þ ) overexpressing human S-endoglin on the vascular endothelium driven by the ICAM-2 promoter. The S-Eng þ mice are fertile, show a normal ratio of male to female littermates and have no specific susceptibility to disease (Velasco et al, 2001). The endoglin heterozygous (Eng þ /À ) mice were first intercrossed with transgenic S-Eng þ mice.…”

Section: Transgenic Expression Of S-endoglin Does Not Rescue the Lethmentioning

confidence: 99%

“…Transgenic mice expressing the human S-endoglin cDNA under the control of the endothelial-specific promoter ICAM-2 (S-Eng þ mice) have been previously described (Velasco et al, 2001). Briefly, transgenic mice were obtained from microinjection of the pICAM-2/S-Eng construct into fertilized C57Bl/ 6xSJL mouse embryos.…”

Section: Rescue Experiments With Genetically Modified Micementioning

confidence: 99%

“…We have studied the effects of vascular S-endoglin overexpression on neovascularization and tumor growth by using a transgenic mouse model (SEng þ ) with targeted expression of human S-endoglin under the control of the ICAM-2 endothelial-specific promoter (Velasco et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Characterization of murine S-endoglin isoform and its effects on tumor development

et al. 2005

View full text Add to dashboard Cite

Endoglin is a transmembrane glycoprotein that acts as an auxiliary receptor for transforming growth factor-b (TGF-b) and modulates cellular responses to this pleiotropic cytokine. Endoglin is strongly expressed in endothelial cells, where it appears to exert a crucial role in vascular development and angiogenesis. Two endoglin isoforms (L and S), differing in their cytoplasmic domains, have been previously characterized in human tissues. We now demonstrate the existence of similar L-and Sendoglin variants in murine tissues with 47 and 35 amino acids, respectively, in their cytoplasmic tail. RT-PCR analysis showed that L is the predominant endoglin isoform expressed in mouse tissues, although S-endoglin mRNA is significantly expressed in liver and lung, as well as in endothelial cell lines. Furthermore, a protein of size equivalent to recombinant S-endoglin expressed in mammalian cells was detected in mouse endothelial cells by Western blot analysis. L-and S-endoglin isoforms can form disulfide-linked heterodimers, as demonstrated by cotransfection of L-and S-endoglin constructs. To address the role of S-endoglin in vivo, an S-Eng þ transgenic mouse model that targets S-endoglin expression to the endothelium was generated. The lethal phenotype of endoglin-null (Eng À/À ) mice was not rescued by breeding S-Eng þ transgenic mice into the endoglin-null background. S-Eng þ mice exhibited reduced tumor growth and neovascularization after transplantation of Lewis lung carcinoma cells. In addition, S-Eng þ mice showed a drastic inhibition of benign papilloma formation when subjected to two-stage chemical skin carcinogenesis. These results point to S-endoglin as an antiangiogenic molecule, in contrast to L-endoglin which is proangiogenic.

show abstract

Section: Transgenic Expression Of S-endoglin Does Not Rescue the Lethmentioning

confidence: 99%

Section: Transgenic Expression Of S-endoglin Does Not Rescue the Lethmentioning

confidence: 99%

Section: Rescue Experiments With Genetically Modified Micementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Characterization of murine S-endoglin isoform and its effects on tumor development

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Immunohistochemical detection of endoglin was performed in deparaffinized human and mouse tissue sections by the Envision plus peroxidase method (Dako A/S, Glostrup, Denmark), as previously reported (Velasco et al, 2001). The reaction product was developed with diaminobenzidine tetrahydrochloride and H 2 O 2 .…”

Section: Antibodies and Immunohistochemical Analysismentioning

confidence: 99%

Expression of the TGF-β coreceptor endoglin in epidermal keratinocytes and its dual role in multistage mouse skin carcinogenesis

et al. 2003

View full text Add to dashboard Cite

Endoglin is an integral membrane glycoprotein primarily expressed in the vascular endothelium, but also found on macrophages and stromal cells. It binds several members of the transforming growth factor (TGF)-b family of growth factors and modulates TGF-b 1 -dependent cellular responses. However, it lacks cytoplasmic signaling motifs and is considered as an auxiliary receptor for TGF-b. We show here that endoglin is expressed in mouse and human epidermis and in skin appendages, such as hair follicles and sweat glands, as determined by immunohistochemistry. In normal interfollicular epidermis, endoglin was restricted to basal keratinocytes and absent in differentiating cells of suprabasal layers. Follicular expression of endoglin was high in hair bulb keratinocytes, but decreased in parts distal from the bulb. To address the role of endoglin in skin carcinogenesis in vivo, Endoglin heterozygous mice were subjected to long-term chemical carcinogenesis treatment. Reduction in endoglin had a dual effect during multistage carcinogenesis, by inhibiting the early appearance of benign papillomas, but increasing malignant progression to highly undifferentiated carcinomas. Our results are strikingly similar to those previously reported for transgenic mice overexpressing TGF-b 1 in the epidermis. These data suggest that endoglin might attenuate TGF-b 1 signaling in normal epidermis and interfere with progression of skin carcinogenesis.

show abstract

Vector Targeting in Gene Therapy

Kawakami

Curiel

2006

Encyclopedia of Molecular Cell Biology and Molecular Medicine

View full text Add to dashboard Cite

Vascular gene transfer driven by endoglin and ICAM-2 endothelial-specific promoters

Cited by 39 publications

References 40 publications

Characterization of murine S-endoglin isoform and its effects on tumor development

Characterization of murine S-endoglin isoform and its effects on tumor development

Expression of the TGF-β coreceptor endoglin in epidermal keratinocytes and its dual role in multistage mouse skin carcinogenesis

Vector Targeting in Gene Therapy

Contact Info

Product

Resources

About