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