Human endothelial cells expressing polyoma middle T induce tumors

Primo, Luca; Roca, Cristina; Ferrandi, Chiara; Lanfrancone, Luisa; Bussolino, Federico

doi:10.1038/sj.onc.1203708

Cited by 25 publications

(21 citation statements)

References 55 publications

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“…These KS-like lesions are of mouse cell origin suggesting that these cells are able to recruit normal vascular cells, a phe-nomenon also observed in mice injected with human cells carrying mT oncogene of polyoma virus [156]. Lesions regress in time and are mediated by specific angiogenic factors produced by the cells.…”

Section: The Role Of Angiogenic Inducers In Kaposi's Sarcomamentioning

confidence: 93%

Interactions between endothelial cells and HIV-1

Bussolino

Mitola

Serini

et al. 2001

The International Journal of Biochemistry &Amp; Cell Biology

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Endothelial cells (EC) participate in inflammatory and immune reactions by producing and responding to soluble mediators. Human immunodeficiency virus (HIV)-1 profoundly alters the features of EC. In some anatomical districts, they are infected by the virus and may represent a relevant reservoir. During lymphomononuclear cell diapedesis, EC activate virus replication in crossing cells. Direct or indirect damage of EC is particularly relevant in central nervous system, where blood-brain barrier perturbation is pivotal in neuronal degeneration. The observed alterations of EC adhesive properties contribute in altered leukocyte traffic from blood to lymphoid organs and tissues and play a role in the onset of immune surveillance alteration. These alterations of EC functions are relevant for the general vasculopathy, which marks the acquired immunodeficiency syndrome, and in particular are instrumental in the pathogenesis of Kaposi's sarcoma. Here we discuss the biological and molecular activation of EC in HIV-1 infection that represents the basis to understand the pathogenesis of HIV-1 associated vascular diseases.

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Section: The Role Of Angiogenic Inducers In Kaposi's Sarcomamentioning

confidence: 93%

Interactions between endothelial cells and HIV-1

Bussolino

Mitola

Serini

et al. 2001

The International Journal of Biochemistry &Amp; Cell Biology

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“…The primers 5Ј-TGGTGCGGCAGA-GGGTG-3Ј (position 2011-2027 from the ATG) and 3Ј-GGGGAACTG-CAAGGTGGTG-5Ј (position 2291-2267) were used to amplify the SH2-cDNA portion corresponding to amino acids 670 -721. The cDNAs of ShcASH2 (32) and VavSH2 domains were Myc-tagged by recombinant polymerase chain reaction in pPCR2.1 vector (Invitrogen) and subsequently subcloned into EcoRI-EcoRI sites of the retroviral vector PINCO (34,35). The two transgene domains and green fluorescence protein (GFP) cDNA were under the control of the long terminal repeat and cytomegalovirus promoters, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…After 72 h of infection, cells were analyzed for GFP expression both under fluorescence microscope and through fluorescence-activated cell sorting analysis (FACS Advantage S. E., BD Biosciences). Immunofluorescence analysis with anti-c-Myc Ab was performed as described previously (35).…”

Section: Methodsmentioning

confidence: 99%

Adaptor ShcA Protein Binds Tyrosine Kinase Tie2 Receptor and Regulates Migration and Sprouting but Not Survival of Endothelial Cells

Audero

Cascone

Maniero

et al. 2004

Journal of Biological Chemistry

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“…BMSVThTERT cells formed small transient tumours, which may be analogous to the transient tumours generated by human ECs transfected with Polyoma middle T antigen (Primo et al, 2000). The latter investigation compared transient EC tumour growth with human haemangiomas, which are benign and undergo spontaneous regression.…”

Section: Malignant Transformation Of Bmecsmentioning

confidence: 99%

Multiple stages of malignant transformation of human endothelial cells modelled by co-expression of telomerase reverse transcriptase, SV40 T antigen and oncogenic N-ras

et al. 2002

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We have modelled multiple stages of malignant transformation of human endothelial cells (ECs) by overexpressing the catalytic subunit of human telomerase (hTERT), together with SV40 T antigen (SV40T) and oncogenic N-ras. Transfection with hTERT alone, led to the immortalization of two out of three cultures of bone marrow-derived ECs (BMECs). One hTERT transduced BMEC culture underwent a long proliferative lag before resuming proliferation. BMECs transfected with hTERT alone were functionally and phenotypically normal. BMECs transfected with SV40T (BMSVTs) had an extended lifespan, but eventually succumbed to crisis. BMSVTs exhibited a partially transformed phenotype, demonstrating growth factor independence, altered antigen expression and forming tiny, infrequent colonies in vitro. Transduction of BMSVTs with hTERT resulted in immortalization of 4 out of 4 cultures. BMSVTs immortalized with hTERT formed large colonies in vitro and small transient tumours in vivo. BMECs coexpressing SV40T, hTERT and N-ras exhibited an overtly transformed phenotype; forming very large colonies with an altered morphology and generating rapidly growing tumours in vivo. These investigations demonstrate transformation of human ECs to an overtly malignant phenotype. This model will be useful for understanding mechanisms underlying vascular and angiogenic neoplasias, as well as for testing drugs designed to curtail aberrant EC growth.

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Human endothelial cells expressing polyoma middle T induce tumors

Cited by 25 publications

References 55 publications

Interactions between endothelial cells and HIV-1

Interactions between endothelial cells and HIV-1

Adaptor ShcA Protein Binds Tyrosine Kinase Tie2 Receptor and Regulates Migration and Sprouting but Not Survival of Endothelial Cells

Multiple stages of malignant transformation of human endothelial cells modelled by co-expression of telomerase reverse transcriptase, SV40 T antigen and oncogenic N-ras

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