Abstract
Solute carrier family 3 member 2 (SLC3A2) has been reported to be highly expressed in a variety of carcinomas. However, the function of SLC3A2 in gastric carcinoma (GC) has not been well explored. Monoclonal antibody (mAb) 3G9, generated from immunogen of various human GC cell lines, has been shown to bind to GC tissues specifically. In this study, we identified the target antigen of mAb 3G9 as SLC3A2, and detected the expression profile of SLC3A2 in a panel of gastric cancer cell lines and GC tumor tissues. We found that the increased expression of SLC3A2 was associated with serosal invasion in GC patients. Knockout of SLC3A2 suppressed the migration and invasion of BGC-823 cells in vitro and in vivo, whereas overexpression of SLC3A2 in NCI-N87 cells promoted the migration and invasion in vitro and in vivo. Mechanistic investigations suggested that MUC1, MUC16 and MUC5B were the downstream genes of SLC3A2 in GC cells. Taken together, our data suggested that SLC3A2 promoted the aggressive phenotype of GC by upregulating several mucin genes expression and may serve as a potential biomarker for diagnosis and target therapy.
Highlights
Gastric cancer (GC) is currently the forth most common malignancy as well as the second leading cause of cancer related deaths worldwide [1]
We had generated a specific Monoclonal antibody (mAb) for gastric cancer, named as mAb 3G9, and the antigen of mAb 3G9 was confirmed as high expression rate in gastric cancer cells and tissues
We confirmed the specific antigen of mAb 3G9 as SLC3A2 by immunoprecipitation followed by mass spectrometry analysis and discuss the role of SLC3A2 on gastric cancer metastasis
Summary
Gastric cancer (GC) is currently the forth most common malignancy as well as the second leading cause of cancer related deaths worldwide [1]. The cell surface molecules identified by (monoclonal antibody) mAbs can be used as biomarkers in clinical detection as well as targets for cancer therapies [4,5]. Candidate hybridomas that produce monoclonal antibodies (mAb) were obtained by selective culture and screening by ELISA using GC cells. I131-labeled 3G9 antibodies can accurately localize the tumors of human gastric cancer xenograft and exhibited anti-tumor effect on gastric cancer, suggesting its potential application as radio imaging reagent to detect primary cancer and metastastic www.impactjournals.com/oncotarget cancer in clinical practice [7,8]. The specific antigen of mAb 3G9 and its effects on cell migration and invasion in gastric cancer required further clarification. We investigated the regulatory role of SLC3A2 in cell proliferation, migration and invasion of GC both in vitro and in vivo. This study may provide new insight for the application of mAb 3G9 and the molecular mechanism underlying gastric cancer migration and invasion
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