A pioneering study from Israel has shed new light on the link between obesity and the aggressiveness of gastric cancer while demonstrating potential therapeutic targets for the disease. Results of the translational research, presented during the Society of Surgical Oncology (SSO) 2023 International Conference on Surgical Cancer Care, highlighted the role of extracellular vesicles from adipocytes, which were associated with increased migration, invasion, and angiogenesis in cancer cells in vitro when taken from obese vs lean patients.¹ Authors of the study noted these findings have the potential to impact the future of gastric cancer treatment and management.

Adi Rubin

“We demonstrated for the first time that extracellular vesicles isolated from primary adipocytes from the omentum of obese patients with gastric cancer promote gastric cancer growth and progression, suggesting a new mechanism linking obesity and gastric cancer aggressiveness mediated by extracellular vesicles,” said lead study author Adi Rubin, a clinical dietitian and MSc student at Sourasky Medical Center, Tel Aviv.

As Dr. Rubin explained, obesity is a growing global health concern and is known to be associated with several types of cancer, including gastric cancer. Adipocytes are active metabolic cells that affect endocrine, inflammatory, and cancerous responses. The omentum is known to support the growth of metastasizing cells. Dr. Rubin and colleagues hypothesized that the crosstalk between the omentum and the tumor may affect its aggressiveness through the secretion of extracellular vesicles.

To test their hypothesis, the researchers used a variety of methods to analyze the effects of extracellular vesicles of adipocytes on the progression of gastric cancer. They collected omentum samples from patients with gastric cancer and isolated adipocytes and their secreted extracellular vesicles. Gastric cancer cells were then treated with these extracellular vesicles to evaluate functional differences in proliferation, invasion, and angiogenesis. The team also explored the expression of epithelial-to-mesenchymal transition (EMT)-related genes and conducted microRNA analysis.

Early Diagnosis, Prognosis, and Therapeutic Targets

The results of the study showed a positive correlation among body mass index, visceral fat content, and gastric cancer omental metastasis. Obese adipocytes/extracellular vesicles were found to enhance the migration, invasion, and angiogenesis of gastric cancer cells compared with lean adipocytes/extracellular vesicles. They also induced the expression of EMT-related genes and reduced the expression of E-cadherin in gastric cancer cells. Furthermore, the researchers identified 40 differentially expressed microRNAs within lean and obese adipocytes/extracellular vesicles.

Dr. Rubin explained the significance of these findings: “Our results suggest that obese adipocytes/extracellular vesicles may lead to a more aggressive disease, and a higher expression level of oncomiR-21 [oncogenic microRNA] in obese adipocytes/extracellular vesicles may explain this observation.”

According to Dr. Rubin, these findings have implications for the understanding of the link between obesity and gastric cancer aggressiveness. Future research in this area may focus on understanding the molecular mechanisms behind the observed effects of adipocytes/extracellular vesicles on gastric cancer cells. Additionally, said Dr. Rubin, researchers could explore the potential use of adipocyte-derived extracellular vesicles as biomarkers for early diagnosis and prognosis of gastric cancer in obese patients.

Finally, investigation into the specific microRNAs differentially expressed in lean and obese adipocytes/extracellular vesicles may provide valuable insights into the regulatory mechanisms of cancer progression in obese individuals. According to Dr. Rubin, these microRNAs may potentially serve as therapeutic targets for the development of novel treatments to combat gastric cancer aggressiveness. 

DISCLOSURE: Ms. Rubin reported no conflicts of interest.

REFERENCE

1. Loewenstein S, Rubin A, Lahat G, et al: Obesity and gastric cancer aggressiveness: A new link. Society of Surgical Oncology 2023 International Conference on Surgical Cancer Care. Abstract 90. Presented March 21, 2023.