A Mimic of the Tumor Microenvironment on GPR۳۰ Gene Expression in Breast Cancer

Introduction: The G-protein coupled receptor ۳۰ (GPR۳۰) gene is a member of the G-protein coupled receptor (GPCR) family; involved in breast, endometrial, and ovarian cancers. Many GPCR receptors that are implicated in several types of human cancers are correlated with increased cell proliferation and tumor progression; especially GPR۳۰ gene. Methods: The breast cancer MCF-۷ and MDA-MB-۲۳۱ cells were cultured with different concentrations of glucose (۵.۵, ۱۱, and ۲۵ mM) under normoxia/hypoxia for ۲۴, ۴۸, and ۷۲ hours. Hypoxia conditions were created with Cobalt (II) chloride at a concentration of ۱۰۰ μM in culture media. The scratch assay techniques were carried out to investigate the migration and finally, gene expression levels of GPR۳۰ mRNA were investigated by quantitative Real-Time polymerase chain reaction. Results: The MDA-MB-۲۳۱ cells adaptation in hypoxic conditions is evident which enables cell survival, whereas it results in cell proliferation in the MCF-۷ cells. The increased expression of GPR۳۰ (P≤۰.۰۰۰۱) was found to be associated with the promoted metastasis in the MDA-MB-۲۳۱ cells, while an inverse relationship was seen between the GPR۳۰ mRNA level and cellular migration in the MCF-۷ cells. We found that hypoxia induces the expression of GPR۳۰ in MDA-MB-۲۳۱ cells, and MCF-۷ cells; exposed to hypoxia, had a heterogeneous expression. Conclusions: Increases /decreases in glucose concentration and hypoxia lead to changes in the expression profiles of cancer cells. The upregulation of GPR۳۰ expression was associated with a higher risk of breast cancer metastasis; demonstrating its importance as an applicant bio-target for cancer therapy.

Keywords:

Breast Neoplasms , Hypoxia , Glucose , GPER۱