HLA-G expression is associated with metastasis and poor survival in the Balb/c nu/nu murine tumor model with ovarian cancer

Aberrant HLA‐G expression is associated with tumor invasiveness and poor clinical prognosis; however, there is a lack of preclinical animal model to address whether HLA‐G plays a causal role in the unfavorable prognosis of malignancies. In the current study, ovarian carcinoma cell lines (HO‐8910 and Ovcar‐3) were transfected with HLA‐G gene. HLA‐G expression was analyzed with western blot and flow cytometry. Transwell experiment was performed to analyze the cell migration and invasion capability and/or multicellular spheroid formation was investigated with the 3D culture assay in vitro. The effects of HLA‐G expression for tumor cell organ metastasis and for mouse survival was analyzed with the Balb/c nu/nu mouse model. Our data showed that HO‐8910‐G and Ovcar‐3‐G cells are of higher invasion potential compared with the parental HO‐8910 and Ovcar‐3 cells. Multicellular spheroid formation exists only in HO‐8910‐G cells in a 3D culture assay. In Balb/c nu/nu mouse model, widespread metastasis was observed in mice xenografted with HO‐8910‐G cells, but not in the group with parental cells. Mouse survival was dramatically decreased in HO‐8910‐G and Ovcar‐3‐G xenografted mice than that with HO‐8910 and Ovcar‐3 cells, respectively. In summary, our study provided the first evidence that HLA‐G expression is associated with tumor metastasis and with poor survival in an animal model with ovarian cancer.