R-spondins are Expressed by Ewing Sarcoma Cells and are Potential Targets for Metastasis Inhibition
Year: 2018
Type: article
Abstract: BackgroundEwing sarcoma is a highly metastatic tumor, and the Wnt/ beta-catenin signaling pathway was recently shown to contribute to the metastatic phenotype.R-spondin (RSPO) ligands potentiate canonical Wnt signaling in human cancers, including Ewing sarcoma cells, by binding to the LGR family of receptor proteins.However, the pattern of RSPO expression in Ewing sarcoma has not previously been defined. Methods Expression ofRSPOs was determined using qRT-PCR in Ewing sarcoma cell lines as well as in tissues that are frequent sites of metastasis in xenograft mouse models.Inhibition of R-spondin 2 (RSPO2) was achieved using the monoclonal antibody OMP130-M230.OMP130-M230 was tested for efficacy in vitro, and its effects on both subcutaneous growth as well as metastasis were examined using in vivo xenograft models.Results RSPOs are expressed by Ewing sarcoma cells and tissues that are frequent sites of metastasis.OMP130-M230 had moderate ability to block RSPO signaling in vitro.In vivo, inhibition of RSPO2 did not affect tumor size, but significantly inhibited the frequency of metastatic nodule formation.Conclusions RSPOs and associated signaling molecules are expressed by Ewing sarcoma cells themselves and also by tissues to which Ewing sarcoma metastasizes.Inhibition of RSPO2 blunts Wnt/beta-catenin signaling response in vitro and reduces formation of metastasis.These studies provide preliminary evidence that RSPOs may be amenable to therapeutic targeting for metastasis inhibition in Ewing sarcoma.
Source: Michigan Journal of Medicine
Institution: University of Michigan
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W2800619360