A recent study from Tokyo University of Agriculture and Technology has developed a new way to study Hemangiosarcoma in the lab. The researchers successfully grew 2.5D organoids using tissue from dogs with HSA and compared them to organoids from benign nodular hyperplasia to identify what makes HSA malignant.
The study’s key finding involves a gene called PLAAT3. This gene was highly active in HSA organoids compared to benign ones. PLAAT3 belongs to a family known to mediate lipid reprogramming in cancer cells, and its upregulation enables membrane-associated protein dysfunction that promotes tumor invasion and migration. When the researchers used siRNA or a chemical inhibitor to block PLAAT3, the HSA cells lost much of their ability to invade, though their growth was only mildly affected. This makes PLAAT3 a promising therapeutic target—attacking it may curb metastasis without the toxicity of broadly killing dividing cells.
The team also created a better mouse model by injecting HSA organoid cells directly into the spleen. Unlike older subcutaneous models that fail to show spread to other organs, this orthotopic model allowed tumors to metastasize to the liver and pancreas, mimicking real disease in dogs. The researchers note that orthotopic models in other cancers tend to show greater metastatic tendency than heterotopic ones, and their findings support this.
Beyond PLAAT3, the study identified other upregulated genes in HSA including HIP1 and MARVELD3, which may play oncogenic roles and warrant further investigation. The authors caution, however, that sample size was limited and larger studies are needed to validate their results.
These findings offer two advances: a new therapeutic target in PLAAT3, and a more realistic laboratory platform for testing drugs. The organoid and xenograft models may help accelerate research for both canine HSA and human angiosarcoma.
