Oncotarget

Research Papers:

Etoposide-Bevacizumab a new strategy against human melanoma cells expressing stem-like traits

Maura Calvani, Francesca Bianchini, Maria Letizia Taddei, Matteo Becatti, Elisa Giannoni, Paola Chiarugi and Lido Calorini _

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Oncotarget. 2016; 7:51138-51149. https://doi.org/10.18632/oncotarget.9939

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Abstract

Maura Calvani1, Francesca Bianchini1, Maria Letizia Taddei1, Matteo Becatti1, Elisa Giannoni1, Paola Chiarugi1,2, Lido Calorini1

1Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy

2Tuscany Tumor Institute and “Center for Research, Transfer and High Education DenoTHE”, 50134, Florence, Italy

Correspondence to:

Lido Calorini, email: [email protected]

Paola Chiarugi, email: [email protected]

Keywords: human melanoma A375 and Hs294T lines, cancer stem-like trait, CD133/VEGF-R2+ melanoma cells, etoposide-bevacizumab cooperation

Received: October 27, 2015     Accepted: May 01, 2016     Published: June 09, 2016

ABSTRACT

Tumors contain a sub-population of self-renewing and expanding cells known as cancer stem cells (CSCs). Putative CSCs were isolated from human melanoma cells of a different aggressiveness, Hs294T and A375 cell lines, grown under hypoxia using “sphere-forming assay”, CD133 surface expression and migration ability. We found that a cell sub-population enriched for P1 sphere-initiating ability and CD133 expression also express larger amount of VEGF-R2. Etoposide does not influence phenotype of this sub-population of melanoma cells, while a combined treatment with Etoposide and Bevacizumab significantly abolished P1 sphere-forming ability, an effect associated with apoptosis of this subset of cells. Hypoxic melanoma cells sorted for VEGF-R2/CD133 positivity also undergo apoptosis when exposed to Etoposide and Bevacizumab. When Etoposide and Bevacizumab-treated hypoxic cells were injected intravenously into immunodeficient mice revealed a reduced capacity to induce lung colonies, which also appear with a longer latency period. Hence, our study indicates that a combined exposure to Etoposide and Bevacizumab targets melanoma cells endowed with stem-like properties and might be considered a novel approach to treat cancer-initiating cells.


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