AUTHOR=Pelizzo Gloria , Riva Federica , Croce Stefania , Avanzini Maria Antonietta , Acquafredda Gloria , de Silvestri Annalisa , Mazzon Emanuela , Bramanti Placido , Zuccotti Gianvincenzo , Mazzini Giuliano , Calcaterra Valeria 

TITLE=Proliferation Pattern of Pediatric Tumor-Derived Mesenchymal Stromal Cells and Role in Cancer Dormancy: A Perspective of Study for Surgical Strategy

JOURNAL=Frontiers in Pediatrics

VOLUME=Volume 9 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2021.766610

DOI=10.3389/fped.2021.766610

ISSN=2296-2360

ABSTRACT=The explanation for cancer recurrence still remains to be fully elucidated, moreover tumor dormancy, which is a process whereby cells enter reversible G0 cell cycle arrest, appears to be a critical step in this phenomenon. We evaluated the cell cycle proliferation pattern in pediatric tumor-derived- mesenchymal stromal cells (MSCs), in order to provide a better understanding of the complex mechanisms underlying cancer dormancy. Specimens were obtained from 14 pediatric patients diagnosed with solid tumors and submitted to surgery. Morphology, phenotype, differentiation, immunological capacity, proliferative growth of tumor-MSCs were studied. Flow cytometric analysis was performed to evaluate the cell percentage of each cell-cycle phase. Healthy donor bone marrow-derived MSCs (BM-MSC) were employed as controls. It was noted that the DNA profile of proliferating BM-MSC was different from that of tumor-MSC. All BM-MSC expressed the typical DNA profile of proliferating cells, while in all tumor-MSC samples ≥70% of cells were detected in the G0/G1 phase. In particular, seven tumor-MSC samples displayed intermediate cell cycle behaviour and the other seven tumor-MSC samples exhibited a slow cell cycle. The increased number of tumor-MSCs in the G0-G1 phase compared to BM-MSCs, supports a role for quiescent MSC in tumor dormancy regulation. Understanding the mechanisms that promote dormant cell cycle arrest is essential to identify predictive markers of recurrence and to promote a dedicated surgical planning.