Small extracellular vesicles: from mediating cancer cell metastasis to therapeutic value in pancreatic cancer

Abstract

Pancreatic cancer is a highly malignant tumor and, is extremely difficult to diagnose and treat. Metastasis is one of the critical steps in the development of cancer and uses cell to cell communication to mediate changes in the microenvironment. Small extracellular vesicles (sEVs)-carry proteins, nucleic acids and other bioactive substances, and are important medium for communication between cells. There are two primary steps in sVEs-mediated metastasis: communication between pancreatic cancer cells and their surrounding microenvironment; and the communication between primary tumor cells and distant organ cells in distant organs that promotes angiogenesis, reshaping extracellular matrix, forming immunosuppressive environment and other ways to form appropriate pre-metastasis niche. Here, we explore the mechanism of localization and metastasis of pancreatic cancer and use sEVs as early biomarkers for the detection and treatment of pancreatic cancer. Graphical Abstract

Exosomal EPHA2 derived from highly metastatic breast cancer cells promotes angiogenesis by activating the AMPK signaling pathway through Ephrin A1-EPHA2 forward signaling

“…Tumor metastasis is a complex multistep process, which requires not only needs tumor cell reprogramming to achieve high metastasis but also remodeling the microenvironment of the distal site to establish a metastatic niche suitable for tumor cell colonization and growth 28 - 30 . Angiogenesis plays a key role in the establishment of metastatic niches 31 - 33 . To promote angiogenesis, tumor cells communicate with stromal cells and educate them to “follow their footsteps,” facilitating the invasion of tumor cells into local circulation to colonize distal regions 34 - 36 .…”

Pancreatic cancer, pancreatogenic diabetes, type 2 diabetes mellitus

“…Еще одно перспективное направления в поиске ранних биомаркеров ПАК базируется на современном представлении об этапности развития патология от предраковых изменений до рака (сроки развития PanINs до прогрессирующего рака варьируют вплоть до 10 лет до диагностики РПЖ) и акцентирует внимание не на активности и метаболизме самих раковых клеток, а на активности «опухолевого окружения» -стромальных клеток [68][69][70][71]. Возможно, что раковые клетки и/или окружающие стромальные клетки, в частности панкреатические звездчатые клетки (доминирующие коллаген-продуцирующие клетки стромы ПАК), секретируют факторы, не только ответственные за регуляцию микроокружения РПЖ и микроокружение метастатических очагов, рост и выживание раковых клеток, их метастическое перемещение [72][73][74][75][76][77][78], но и опосредующие развитие инсулинорезистентности и гипергликемии [79][80][81]. Perera CJ с соавт.…”