27P - Common gene signature expressed by breast and kidney cancers-derived endothelial colony forming cells

Date 07 May 2015
Event IMPAKT 2015
Session Welcome reception and Poster Walk
Topics Renal Cell Cancer
Breast Cancer
Translational Research
Presenter Richard Tancredi
Citation Annals of Oncology (2015) 26 (suppl_3): 10-14. 10.1093/annonc/mdv116
Authors R. Tancredi1, V. Fotia1, F. Moccia2, V. Rosti3, C. Porta4, M.G. Della Porta5, L. Beltrame6, A. Zambelli7, G.A. Da Prada1, A. Riccardi8
  • 1Medical Oncology Unit, Fondazione S. Maugeri IRCCS, 27100 - Pavia/IT
  • 2Laboratory Of General Physiology, University of Pavia, 27100 - Pavia/IT
  • 3Center For The Study And The Treatment Of Myelofibrosis, Research Laboratories, Ospedale San Matteo, 27100 - Pavia/IT
  • 4Oncologia Medica, Ospedale San Matteo, 27100 - Pavia/IT
  • 5Hematology And Oncology, Ospedale San Matteo, 27100 - Pavia/IT
  • 6Farmacologia Antitumorale Genomica Traslazionale, Istituto Mario Negri, Milano/IT
  • 7Oncologia Medica, Azienda Ospedaliera Papa Giovanni XXIII, 24127 - Bergamo/IT
  • 8Medical Oncology Unit, Fondazione S. Maugeri IRCCS, Pavia/IT

Abstract

Body

Inhibitors of the vascular endothelial growth factor (VEGF) pathway are approved for the treatment of several tumor types but their effectiveness is limited. The heterogeneity of tumor endothelial cells, determined by the dynamics of tumor vascularization not only requires sprouting angiogenesis but impinges on alternative mechanisms such as the recruitment of bone marrow (BM)-derived endothelial progenitor cells (EPCs). We focused on endothelial colony forming cells (ECFCs) the only EPC population truly belonging to the endothelial lineage by comparing normal vs tumor-derived ECFCs phenotype in two distinct, but hypervascularized cancers, such as renal cell carcinoma (RCC) and breast cancer (BC). ECFCs were successfully isolated from healthy donors (N-ECFCs), RCC patients (RCC-ECFCs) and BC patients (BC-ECFCs). ECFC colonies displayed the typical cobblestone-shaped monolayer, both normal and tumor derived ECFCs formed capillary-likes structures, and express classic endothelial markers. There was no difference in growth kinetics or tubulogenic rate between N-, RCC-, and BC-ECFCs. However, RCC-ECFCs were more resistant to rapamycin-induced apoptosis as compared to control cells, while BC-ECFCs were more sensitive. Genomic expression analysis identified a total of 382 differentially expressed genes (DEGs) between N- and BC-ECFCs and of 71 DEGs (33 up-regulated, 38 down-regulated) between N- and RCC-ECFCs. Nevertheless, we identified a common gene signature in BC- and RCC-derived ECFCs due to the presence of 35 DEGs that shared the same direction of regulation, i.e. all genes were either up-regulated or down-regulated in both groups. Ingenuity pathway analysis (IPA) unveiled interactions between these 35 DEGs there were centered on FOS, which plays a key role in the control of cell cycle and apoptosis. These findings provide the first strong molecular evidence that tumor microenviroment may also affect distant tissues and reprogram bone marrow derived-cells, such as ECFCs. However, the common signature identified in ECFCs isolated from patients suffering from two distinct tumor types might be relevant for carcinogenesis and could suggest new targets anti-angiogenic therapies.

Disclosure: All authors have declared no conflicts of interest.