Parasitic protein from Schistosoma could help combat hepatocellular carcinoma

Cancer News: Researchers from China have recently discovered a remarkable breakthrough in liver cancer treatment. A team from the Shanghai Veterinary Research Institute and the Lanzhou Veterinary Research Institute have unveiled that a parasitic protein from Schistosoma japonicum, a parasite known for causing liver fibrosis, may have potential anti-cancer properties. This Cancer News report will explore how this breakthrough could lead to novel treatments for hepatocellular carcinoma (HCC), a highly deadly form of liver cancer.


Parasitic protein from Schistosoma could help combat hepatocellular carcinoma

Understanding Liver Fibrosis and Liver Cancer
Liver fibrosis is a common precursor to hepatocellular carcinoma, a form of liver cancer. Fibrosis develops as a result of chronic liver damage and can lead to cirrhosis, ultimately increasing the risk of developing cancer. The link between liver fibrosis and HCC has been well established, but treatments for liver fibrosis and early-stage liver cancer remain limited and largely ineffective.
 
The study delves into how parasitic infections, which are typically harmful to humans, may be exploited to develop new therapies against liver cancer.
 
Schistosoma Parasites and Their Role in Liver Fibrosis
Schistosomiasis is a parasitic disease that affects millions of people in tropical regions. The disease, caused by Schistosoma japonicum among other species, primarily impacts the liver. Chronic infection leads to the development of liver fibrosis, a condition where excessive scar tissue forms in response to the parasite's presence in the liver. While this fibrosis can be harmful, recent studies have found that some proteins from the parasite may actually help regulate the growth of liver cells.
 
Previous research from the same institutions showed that proteins and microRNAs (miRNAs) from Schistosoma japonicum have anti-fibrotic properties. These proteins, delivered to liver cells via the parasite's extracellular vesicles (EVs), regulate genes that control fibrosis, preventing excessive scarring.
 
The Discovery of sja-let-7 and Its Role in Liver Cancer
In their most recent study, the team focused on a specific miRNA known as sja-let-7, which is delivered to liver cells by Schistosoma japonicum. This molecule was previously known for its ability to reduce liver fibrosis, but the researchers have now demonstrated its potential to suppress liver cancer as well.
 
The researchers found that sja-let-7 targets a gene called Col1α2, which is known to promote liver fibrosis. By suppressing this gene, sja-let-7 inhibits the growth and spread of liver cancer cells. Their experiments on both liver fibrosis models and liver cancer cell lines revealed that introducing sja-let-7 significantly reduced the proliferation and migration of cancer cells.
 
The study showed that sja-let-7 had a dual effect. It not only reduced fibrosis but also slowed the growth of hepatocellular carcinoma cells. According to the study, introducing sja-let-7 to liver cancer cells reduced cell proliferation by over 26% and inhibited cancer cell migration by more than 42%. These findings suggest that sja-let-7 could serve as a potential therapeutic agent against HCC by inhibiting fibrosis and cancer progression simultaneously.
 
Key Findings from the Study
-Col1α2 Expression and Cancer Growth: The study found that the Col1α2 gene, which is associated with fibrosis, was highly expressed in liver cancer cells. The research revealed that reducing the expression of this gene could lead to a significant decrease in cancer cell growth and migration.
 
-Anti-Tumor Effects of sja-let-7: The team demonstrated that sja-let-7 can inhibit cancer progression by directly targeting Col1α2. In tests on liver cancer cell lines, the miRNA reduced cancer cell proliferation and colony formation. Additionally, the study showed that sja-let-7 could inhibit the movement of cancer cells, which is essential in preventing the spread of cancer.
 
-Involvement of the TGF-β/SMAD Pathway: The study also explored how sja-let-7 interacts with the TGF-β/SMAD signaling pathway, which plays a crucial role in regulating cell growth and fibrosis. By targeting this pathway, sja-let-7 reduces the activity of TGF-β and its related proteins, further suppressing tumor development.
 
-Diagnostic Potential of Col1α2: Beyond its therapeutic potential, the study suggested that Col1α2 could also serve as a biomarker for diagnosing liver cancer. Analysis of cancer patient data indicated that higher levels of Col1α2 expression were linked to worse outcomes and more aggressive forms of the disease. The researchers proposed that monitoring Col1α2 levels could help identify patients at risk for developing liver cancer.
 
The Promise of Helminth-Derived Therapies
The implications of this study are profound. The idea that a parasitic infection could produce molecules with therapeutic benefits aligns with the broader “hygiene hypothesis.” This theory posits that certain parasitic infections may have evolved to modulate the human immune system, potentially preventing autoimmune diseases and other conditions.
 
The study also highlights the therapeutic potential of helminth-derived substances in treating cancer. Although helminthic therapy is still a controversial and experimental field, this research adds to the growing body of evidence that parasites, traditionally viewed as harmful, may hold the key to developing new treatments for diseases like cancer.
 
Future Directions and Challenges
Despite the exciting findings, several challenges remain. The experiments conducted were primarily in vitro, meaning they were done in a laboratory setting rather than in living organisms. While the results are promising, further studies using animal models are needed to determine whether sja-let-7 can effectively reduce liver cancer in vivo.
 
Additionally, more research is required to understand the full range of effects sja-let-7 might have in the body. Since it is delivered by a parasite, there may be unintended consequences or off-target effects that need to be addressed before the miRNA can be considered a viable treatment.
 
Finally, researchers will need to explore how sja-let-7 can be delivered to patients in a clinical setting. Developing a safe and effective method for administering the miRNA without causing harm will be a critical step in moving this therapy from the lab to the clinic.
 
Conclusion
The discovery of sja-let-7's anti-tumor properties opens up exciting new avenues for liver cancer treatment. By targeting the Col1α2 gene, this miRNA not only reduces liver fibrosis but also inhibits the growth and spread of liver cancer cells. While further research is needed, the findings from this study could eventually lead to the development of new treatments for hepatocellular carcinoma, offering hope to millions of patients worldwide.
 
The study findings were published in the peer-reviewed journal: Genes.
https://www.mdpi.com/2073-4425/15/9/1165
 
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