Breast and renal cancer—Derived endothelial colony forming cells share a common gene signature

Autor: Sergio Marchini, Gian Antonio Da Prada, Paolo Pedrazzoli, Vittoria Fotia, Francesco Moccia, Matteo G. Della Porta, Maurizio D'Incalci, Alberto Zambelli, Elisa Bonetti, Alberto Riccardi, Luca Beltrame, Vittorio Rosti, Richard Tancredi, Camillo Porta, Valentina Poletto, Giulia Gallizzi
Rok vydání: 2017
Předmět:
Zdroj: European Journal of Cancer. 77:155-164
ISSN: 0959-8049
DOI: 10.1016/j.ejca.2017.01.025
Popis: Background Neovascularisation supports the metastatic switch in many aggressive solid cancers. Tumour neovessels are mostly lined by endothelial cells sprouting from nearby capillaries, but they could also be contributed by circulating endothelial progenitor cells (EPCs). However, scant information is available about tumour-derived EPCs. Methods We carried out the first thorough, unbiased comparison of phenotype, function and genotype of normal versus tumour-derived endothelial colony forming cells (ECFCs), a truly endothelial EPC subtype. We used healthy donors–derived ECFCs (N-ECFCs) as control for breast cancer (BC)– and renal cell carcinoma (RCC)–derived ECFCs. Results We found that both BC- and RCC-ECFCs belong to the endothelial lineage. Normal and tumour-derived ECFCs did not differ in terms of proliferative and tubulogenic rates. However, RCC-ECFCs were more resistant to rapamycin-induced apoptosis, whereas BC-ECFCs were more sensitive as compared with N-ECFCs. Gene expression profiling revealed 382 differentially expressed genes (DEGs; 192 upregulated and 150 downregulated) and 71 DEGs (33 upregulated, 38 downregulated) when comparing, respectively, BC- and RCC-ECFCs with N-ECFCs. Nonetheless, BC- and RCC-derived ECFCs shared 35 DEGs, 10 of which were validated by qRT-PCR; such 35 DEGs are organised in a gene network centred on FOS. Conclusion These results provide the first clear-cut evidence that BC- and RCC-derived ECFCs exhibit an altered gene expression profile as compared with N-ECFCs; yet, they share a common gene signature that could highlight novel and more specific targets to suppress tumour vascularisation.
Databáze: OpenAIRE