Role of diabetes-related inflammation in pancreatic cancer evaluated by aptamer-based detection of circulating tumor cells in a streptozotocin-induced Panc02-transplanted murine model.

Backgrounds/aims: Diabetes is a recognized risk factor for pancreatic cancer; however, precise molecular mechanisms remain unclear. This study aimed to assess the influence of inflammation on the progression of pancreatic cancer in a diabetic murine model utilizing circulating tumor cells (CTC).

Methods: Fifty mice were randomly allocated into five groups. The P group were injected Panc02 cells only. In the streptozotocin (STZ), STZ/P, and P/STZ groups, mice were administered intraperitoneal STZ solution (50 mg/kg) alone, prior to Panc02 cell injection, and following Panc02 cell injection, respectively. Tumor development was assessed by gross inspection. Immunohistochemistry was performed to evaluate inflammatory cytokine expression, and CTCs were detected using quantum dot-conjugated aptamers.

Results: All mice exposed to STZ developed marked hyperglycemia. Tumor volume to body weight ratio was significantly higher in both P/STZ and STZ/P groups (p < 0.001). Liver metastasis rate was highest in the P/STZ group (p = 0.05). Malondialdehyde (p < 0.001), interleukin-1β (p < 0.05), tumor necrosis factor-α (p < 0.001), and interleukin-6 (p < 0.05) levels were significantly elevated in the STZ/P group. Expression of Signal Transducer and Activator of Transcription 3 and Snail1 was increased in both STZ/P and P/STZ groups. In addition, seven mice in the STZ/P group (70%) and nine mice in the P/STZ group (90%) exhibited larger CTC-like cells (p < 0.001).

Conclusions: In STZ-induced murine models, both hyperglycemia and elevated inflammatory markers were observed. Within this diabetes-associated inflammatory microenvironment, pancreatic cancer cells demonstrated increased proliferation and metastasis, as verified by aptasensor-based CTC detection.