TY - JOUR
T1 - Breast and renal cancer—Derived endothelial colony forming cells share a common gene signature
AU - Moccia, Francesco
AU - Fotia, Vittoria
AU - Tancredi, Richard
AU - Della Porta, Matteo Giovanni
AU - Rosti, Vittorio
AU - Bonetti, Elisa
AU - Poletto, Valentina
AU - Marchini, Sergio
AU - Beltrame, Luca
AU - Gallizzi, Giulia
AU - Da Prada, Gian Antonio
AU - Pedrazzoli, Paolo
AU - Riccardi, Alberto
AU - Porta, Camillo
AU - Zambelli, Alberto
AU - D'Incalci, Maurizio
PY - 2017/5/1
Y1 - 2017/5/1
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Endothelial progenitor cells
KW - Gene profiling
KW - Renal cell carcinoma
KW - Tumour vascularisation
UR - http://www.scopus.com/inward/record.url?scp=85014023203&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85014023203&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2017.01.025
DO - 10.1016/j.ejca.2017.01.025
M3 - Article
AN - SCOPUS:85014023203
VL - 77
SP - 155
EP - 164
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
ER -