Anti ‐tumor effects of an antagonistic mAb against the ASCT2 amino acid transporter on KRAS‐mutated human colorectal cancer cells

This study strongly suggests that ASCT2 is an excellent target molecule for the treatment of malignancies, especiallyKRAS‐mutated cancers. AbstractKRAS mutations are detected in numerous human cancers, but there are few effective drugs forKRAS‐mutated cancers. Transporters for amino acids and glucose are highly expressed on cancer cells, possibly to maintain rapid cell growth and metabolism. Alanine‐serine‐cysteine transporter 2 (ASCT2) is a primary transporter for glutamine in cancer cells. In this study, we developed a novel mono clonal antibody (mAb) recognizing the extracellular domain of human ASCT2, and investigated whether ASCT2 can be a therapeutic target forKRAS‐mutated cancers. Rats were immunized with RH7777 rat hepatoma cells expressing human ASCT2 fused to green fluorescent protein (GFP). Splenocytes from the immunized rats were fused with P3X63Ag8.653 mouse myeloma cells, and selected and cloned hybridoma cells secreting Ab3‐8 mAb were established . This mAb reacted with RH7777 transfectants expressing ASCT2‐GFP proteins in a GFP intensity‐dependent manner. Ab3‐8 reacted with various human cancer cells, but not with non‐cancer breast epithelial cells orASCT2‐knocked out HEK293 and SW1116 cells. In SW1116 and HCT116 human colon cancer cells withKRAS mutations, treatment with Ab3 ‐8 reduced intracellular glutamine transport, phosphorylation of AKT and ERK, and inhibited in vivo tumor growth of these cells in athymic mice. Inhibition of in v...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research