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Recent Advances in Basic Pancreatic Cancer Research

Toshiyuki Ishiwata, M.D., Ph.D.   

Team Leader (Geriatric Pathology)

Pancreatic cancer is one of the most lethal human malignancies. The prevalence of this cancer is increased in older people. The difficulties in early detection and curative treatment of pancreatic cancer, and the rapidly growing aging society predict an imminent increase in pancreatic cancer-related deaths. We reported that telomere length is shorter in pre-cancerous lesions than in healthy pancreatic duct. To find early-stage pancreatic cancer patients, we are trying to develop a method to measure telomere length using blood cells. Pancreatic cancers aggressively invade adjacent tissues and metastasize to distant organs. We found that nestin, a neuroepithelial stem cell marker, and H19, a long non-coding RNA, correlate to pancreatic cancer metastasis. Transplantation of pancreatic cancer cells with lower nestin or H19 levels formed fewer metastases in immunodeficient mice. Recent studies have shown that pancreatic cancer is a heterogeneous tumor. Using 3D culturing, we found morphologically immature pancreatic cancer stem cell-like cells with a smooth cell surface and fewer intracytoplasmic organelles. We recently reported that there are pancreatic cancer cell types with epithelial and mesenchymal features. The 3D culturing method enhances the morphological and functional differences of these cancer cell types. Currently, we are investigating synchronizing heterogeneous pancreatic cancer cells to similar cell types. This may lead to increasing the efficacy of anti-cancer drugs and fewer metastases. We would like to collaborate with researchers in various areas to advance pancreatic cancer research.