Etoposide-Bevacizumab a new strategy against human melanoma cells expressing stem-like traits.
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.
Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy.
Maura
M
Calvani
Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy.
Francesca
F
Bianchini
Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy.
Maria Letizia
ML
Taddei
Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy.
Matteo
M
Becatti
Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy.
Elisa
E
Giannoni
Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy.|Tuscany Tumor Institute and "Center for Research, Transfer and High Education DenoTHE", 50134, Florence, Italy.
Paola
P
Chiarugi
Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134, Florence, Italy.
Lido
L
Calorini
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005047:Etoposide / Q000008:administration & dosage*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000517:prevention & control; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D000068258:Bevacizumab; D005047:Etoposide
CD133/VEGF-R2+ melanoma cells; Etoposide-Bevacizumab cooperation; cancer stem-like trait; human melanoma A375 and Hs294T lines