The Intrinsic and Extrinsic Implications of RANKL/RANK Signaling in Osteosarcoma: From Tumor Initiation to Lung Metastases.

Cancers (Basel) 2018 Oct 24;10(11). Epub 2018 Oct 24.

INSERM, UMR 1238, Faculté de Médecine, Université de Nantes, F-44035 Nantes, France.

Osteosarcoma is the most frequent form of malignant pediatric bone tumor. Despite the current therapeutic arsenal, patient life-expectancy remains low if metastases are detected at the time of diagnosis, justifying research into better knowledge at all stages of osteosarcoma ontogenesis and identification of new therapeutic targets. Receptor Activator of Nuclear factor κB (RANK)expression has been reported in osteosarcoma cells, raising the question of Receptor Activator of Nuclear factor κB Ligand (RANKL)/RANK signaling implications in these tumor cells (intrinsic), in addition to previously reported implications through osteoclast activation in the tumor microenvironment (extrinsic). Based on in vitro and in vivo experimentations using human and mouse osteosarcoma cell lines, the consequences on the main cellular processes of RANK expression in osteosarcoma cells were analyzed. The results revealed that RANK expression had no impact on cell proliferation and tumor growth, but stimulated cellular differentiation and, in an immune-compromised environment, increased the number of lung metastases. The analysis of RANKL, RANK and osteoprotegerin (OPG) expressions in biopsies of a cohort of patients revealed that while RANK expression in osteosarcoma cells was not significantly different between patients with or without metastases at the time of diagnosis, the OPG/RANK ratio decreased significantly. Altogether, these results are in favor of RANKL-RANK signaling inhibition as an adjuvant for the treatment of osteosarcoma.

Download full-text PDF

Source
http://www.mdpi.com/2072-6694/10/11/398
Publisher Site
http://dx.doi.org/10.3390/cancers10110398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265790PMC
October 2018

Publication Analysis

Top Keywords

rank expression
12
osteosarcoma cells
12
factor κb
8
expression osteosarcoma
8
time diagnosis
8
revealed rank
8
lung metastases
8
activator nuclear
8
nuclear factor
8
receptor activator
8
rankl/rank signaling
8
osteosarcoma
8
tumor
5
tumor cells
4
addition reported
4
intrinsic addition
4
reported implications
4
cells intrinsic
4
osteoclast activation
4
expressions biopsies
4

Similar Publications