Post-surgery fluids promote transition of cancer stem cell- to-endothelial and AKT/mTOR activity, contributing to relapse of giant cell tumors of bone

Flavio Fazioli, Gianluca Colella, Roberta Miceli, Mariano Giuseppe Di Salvatore, Michele Gallo, Serena Boccella, Annarosaria De Chiara, Carlo Ruosi, Filomena de Nigris

Research output: Contribution to journalArticle

Abstract

Giant cell tumors of bone (GCTB) are rare sarcomas with a high rate of unpredictable local relapse. Studies suggest that surgical methods affect recurrence, supporting the idea that local disease develops from re-growth of residual cancer cells. To identify early prognostic markers of individual risk of recurrence, we evaluated the effect of post-surgery fluids from a cohort of GCTB patients on growth of primary and established sarcoma cell lines, and mice xenographts. Post-surgery fluids increased cell growth and enhanced expression of CD44++, the principal receptor for the extracellular matrix component hyaluronan and the mesenchymal stem marker CD117+. Cancer cells became highly invasive and tumorigenic, acquiring stemness properties, and activated AKT/mTOR pathway. Prolonged stimulation with post-surgery fluids down-regulated the mesenchymal gene TWIST1 and Vimentin protein, and transdifferentiated cells into tubule-like structures positive to the endothelial markers VE-Cadherin and CD31+. In mice, post-surgery fluids gave rise to larger and more vascularized tumors than control, while in patients AKT/mTOR pathway activation was associated with recurrence by logistic regression (Kaplan-Meier; P<0.001). These findings indicate that post-surgery fluids are an adjuvant in mechanisms of tumor regrowth, increasing stem cell growth and AKT/mTOR activity.

Original languageEnglish
JournalOncotarget
DOIs
Publication statusPublished - 2017

Keywords

  • Journal Article

Fingerprint Dive into the research topics of 'Post-surgery fluids promote transition of cancer stem cell- to-endothelial and AKT/mTOR activity, contributing to relapse of giant cell tumors of bone'. Together they form a unique fingerprint.

  • Cite this