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The interaction between KDR and interleukin-3 receptor (IL-3R) beta common modulates tumor neovascularization

Oncogene volume 24, pages 6394–6405 (2005)Cite this article

Abstract

As vascular endothelial growth factor (VEGF), interleukin-3 (IL-3), released into the tumor microenvironment stimulates motogenic and mitogenic activity of normal and transformed cells. In the present study, we investigate the effects of IL-3 and VEGF on neoplastic vascular growth. Engagement of IL-3 receptor β common (IL-3R βc) contributes to both IL-3- and VEGF-induced Rac1 activation, cell migration and in vitro tube-like structure formation as shown by the expression of the dominant-negative IL-3R βc construct (Δ455). In normal and transformed endothelial cells (EC) as well as in HEK 293 cells expressing KDR and IL-3R, VEGF and IL-3 treatment induces the formation of a KDR/IL-3R βc complex. Moreover, as shown by the IL-3R Δ455 mutant or by the kinase dead KDR, functional receptors are required for this interaction. Consistent with the contribution of IL-3R βc in both IL-3- and VEGF-mediated angiogenic signal, a reduced number of vessels inside tumors are found in mice injected with cells expressing the IL-3R Δ455 mutant. Thus, these findings provide a novel mechanism through which IL-3 and VEGF support cell survival and tumor neovascularization.

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Acknowledgements

We thank Dr BI Terman for providing us wild-type KDR construct. We also thank Professor G Camussi for his helpful advice. This work was supported by grants of the Italian Association for Cancer Research (AIRC) to PD and MFB, MIUR (Ministero dell’Università e Ricerca Scientifica, cofinanziamento MURST and fondi ex-60%) to PD and LP and Special project ‘Oncology’, Compagnia San Paolo/FIRMS, Torino, Italy, to PD.

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Authors and Affiliations

  1. Department of Internal Medicine University of Torino, Corso Dogliotti 14, Torino, 10126, Italy

    Patrizia Dentelli, Arturo Rosso, Giovanni Garbarino, Cristina Calvi, Emanuela Lombard, Luigi Pegoraro & Maria Felice Brizzi

  2. Department of Genetics, Biology and Biochemistry University of Torino, Via Santena 5 bis, Torino, 10126, Italy

    Paola Di Stefano & Paola Defilippi

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  1. Patrizia Dentelli
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  2. Arturo Rosso
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Correspondence to Maria Felice Brizzi.

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Dentelli, P., Rosso, A., Garbarino, G. et al. The interaction between KDR and interleukin-3 receptor (IL-3R) beta common modulates tumor neovascularization. Oncogene 24, 6394–6405 (2005). https://doi.org/10.1038/sj.onc.1208786

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