title: Breast and renal cancer-Derived endothelial colony forming cells share a common gene signature.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Laboratory of General Physiology, Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, Pavia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Moccia
authors.affiliation: PhD Program in Experimental Medicine, University of Pavia, Pavia, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Fotia
authors.affiliation: Medical Oncology Unit, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy.
authors.forename: Richard
authors.initials: R
authors.lastname: Tancredi
authors.affiliation: Cancer Center - IRCCS Humanitas Research Hospital Department of Biomedical Sciences, Humanitas University Rozzano - Milan, Italy.
authors.forename: Matteo Giovanni
authors.initials: MG
authors.lastname: Della Porta
authors.affiliation: Center for the Study of Myelofibrosis S.C. Research and Experimental Laboratory Biotechnology Area IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Rosti
authors.affiliation: Center for the Study of Myelofibrosis S.C. Research and Experimental Laboratory Biotechnology Area IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Bonetti
authors.affiliation: Center for the Study of Myelofibrosis S.C. Research and Experimental Laboratory Biotechnology Area IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Poletto
authors.affiliation: Dept. of Oncology, IRCCS-Mario Negri Institute for Pharmacological Research, Milano, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Marchini
authors.affiliation: Dept. of Oncology, IRCCS-Mario Negri Institute for Pharmacological Research, Milano, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Beltrame
authors.affiliation: Oncology Unit Ospedale SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Gallizzi
authors.affiliation: Medical Oncology Unit, IRCCS Salvatore Maugeri Foundation, Pavia, Italy.
authors.forename: Gian Antonio
authors.initials: GA
authors.lastname: Da Prada
authors.affiliation: Medical Oncology, IRCCS San Matteo University Hospital Foundation, Pavia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Pedrazzoli
authors.affiliation: Medical Oncology Unit, IRCCS Salvatore Maugeri Foundation, Pavia, Italy; Department of Internal Medicine, University of Pavia, Pavia, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Riccardi
authors.affiliation: Medical Oncology, IRCCS San Matteo University Hospital Foundation, Pavia, Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
authors.affiliation: Unit of Medical Oncology, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Zambelli
authors.affiliation: Dept. of Oncology, IRCCS-Mario Negri Institute for Pharmacological Research, Milano, Italy. Electronic address: maurizio.dincalci@marionegri.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'Incalci
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000071960:Breast Carcinoma In Situ / Q000235:genetics*; D001943:Breast Neoplasms / Q000098:blood supply / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D066026:Endothelial Progenitor Cells / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics; D010641:Phenotype; D020123:Sirolimus / Q000494:pharmacology; D059467:Transcriptome; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics
chemical_list: D000903:Antibiotics, Antineoplastic; D020123:Sirolimus
keywords: Breast cancer; Endothelial progenitor cells; Gene profiling; Renal cell carcinoma; Tumour vascularisation