The role of Ng2/Cspg4 in soft tissues sarcoma

ABSTRACT: NG2/CSPG4 is expressed in soft tissue sarcomas, however, its function in this tumor type, and its capacity to serve as a therapeutic target are unknown. Here, we used genetically engineered mice and cells from human tumors to determine the function of Ng2/Cspg4 in soft tissue sarcoma initiation and growth. We also investigated the potential for NG2/CSPG4 mAb immunotherapy to target human sarcomas established as xenografts in mice. Inhibiting Ng2/Cspg4 expression in established soft tissue sarcomas is associated with a smaller tumor volume and a reduction in cell proliferation. Intriguingly, deleting Ng2/Cspg4 at the time of tumor initiation has the opposite effect. Gene profiling found that Igfbp3/5 are substantially downregulated when Ng2/Cspg4 is depleted at the time of tumor initiation, but upregulated or only minimally downregulated when Ng2/Cspg4 is depleted after tumor initiation. Furthermore, the normal regulation of Igfbp is blunted when Ng2/Cspg4 is deleted at the time of tumor initiation. Our data show a difference in NG2/CSPG4 function in tumor initiation and maintenance, and provides pre-clinical evidence supporting NG2/CSPG4 as a therapeutic approach in soft tissue sarcoma.

ORGANISM(S): Mus musculus

PROVIDER: GSE97489 | GEO | 2017/04/07

SECONDARY ACCESSION(S): PRJNA381973

REPOSITORIES: GEO