Targeting glutamine metabolism offers new hope for synovial sarcoma treatment

Synovial sarcoma is an aggressive malignant tumor that primarily affects the limbs of teenagers and young adults. While it can be cured if completely removed by surgery, recurrence or metastasis, the spread of cancer to organs such as the lungs, can make treatment difficult and life-threatening. This may also render radiation and chemotherapy ineffective. Therefore, current treatments alone are insufficient, and new treatments are needed.

Fortunately, cancer research has changed focus and now theorizes new solutions in energy metabolism, asking "What nutrients do cancer cells rely on to survive?" Cancer cells require more nutrients than normal cells and are known to be particularly dependent on the amino acid glutamine, but it hasn't been fully understood whether this could be targeted for treatment.

To test this, Graduate School of Medicine student, Tran Duc Thanh, and Dr. Naoki Takada at Osaka Metropolitan University led a research team to examine the effects of the glutamine metabolism inhibitor, V9302, and glutamine deprivation on lab-grown synovial sarcoma (HS-SY-II) cells and tissue from synovial sarcoma patients. The samples were analyzed using CCK8 assay, Apoptosis assay, immunohistochemical, and Western Blotting analyses. Further, mouse models were induced via injection of HS-SY-II cells and separated into control and V9302 treatment groups.

The team found that ASCT2, a transporter for glutamine uptake, is expressed more in synovial sarcoma than in other types of sarcomas, suggesting that synovial sarcoma may actively take up glutamine. Furthermore, when a V9302 that specifically targets and inhibits ASCT2 was used, the synovial sarcoma cells became less able to proliferate and underwent apoptosis. In contrast, it had relatively little effect on normal cells, suggesting the potential for selective targeting of cancer cells.

In the in vivo experiment, mice administered with V9302 showed suppressed tumor growth. It also did not exhibit severe side effects, such as weight loss or liver and kidney damage.

This study demonstrated that synovial sarcoma strongly depends on glutamine and that treatment blocking ASCT2 holds promise. This will lead to the development of new treatments that not only target cancer cells directly with anticancer drugs, but also weaken cancer by cutting off its nutrient supply."

Tran Duc Thanh, Osaka Metropolitan University

"However, since this research primarily involves experiments on cells and mice, we still need to investigate whether the same effect occurs in other cases of synovial sarcoma, whether it is safe for human use, and what the optimal application method is," Dr. Takada concluded.

The study was published in Cancers.