Exosomes: the key of sophisticated cell–cell communication and targeted metastasis in pancreatic cancer

Abstract

Pancreatic cancer is one of the most common malignancies. Unfortunately, the lack of effective methods of treatment and diagnosis has led to poor prognosis coupled with a very high mortality rate. So far, the pathogenesis and progression mechanisms of pancreatic cancer have been poorly characterized. Exosomes are small vesicles secreted by most cells, contain lipids, proteins, and nucleic acids, and are involved in diverse functions such as intercellular communications, biological processes, and cell signaling. In pancreatic cancer, exosomes are enriched with multiple signaling molecules that mediate intercellular communication with control of immune suppression, mutual promotion between pancreas stellate cells and pancreatic cancer cells, and reprogramming of normal cells. In addition, exosomes can regulate the pancreatic cancer microenvironment and promote the growth and survival of pancreatic cancer. Exosomes can also build pre-metastatic micro-ecological niches and facilitate the targeting of pancreatic cancer. The ability of exosomes to load cargo and target allows them to be of great clinical value as a biomarker mediator for targeted drugs in pancreatic cancer.

Nanoparticle-Labeled Exosomes as Theranostic Agents: A Review

“…46 Moreover, drug conjugated AuNPs have a faster drug release. 39 Therefore, drug delivery vehicles that address these issues are still strongly needed. 47,48 The integration of exosomes, the natural NPs, with artificial NPs has become of high interest in the fields of disease diagnostics and treatment due to the exosomes' excellent biocompatibility, long-term circulation, and nonimmunogenicity, which makes them ideal to deliver different types of drugs, RNAs, and proteins.…”

“…Exosomes have a major role in cellular communication. The cells are able to communicate between each other by the exchange of exosomes and their cargo. − Exosomes also have a significant potential benefit in the diagnosis and treatment of cancer . The exosome-based system has been advanced to deliver the cancer drugs doxorubicin and paclitaxel, as well as RNAs and enzymes, to targeted cancer cells. , Engineering exosomes with dual ligand functionality is essential to increase their therapeutic efficiency.…”

“…For example, when it comes to using NPs for a targeted photothermal therapy, most of the NPs such as QDs and IONPs require a high temperature of ∼50 °C that causes damage to the surrounding healthy tissue. , In addition, several researchers have confirmed the cytotoxicity of QDs . Moreover, drug conjugated AuNPs have a faster drug release . Therefore, drug delivery vehicles that address these issues are still strongly needed. , The integration of exosomes, the natural NPs, with artificial NPs has become of high interest in the fields of disease diagnostics and treatment due to the exosomes’ excellent biocompatibility, long-term circulation, and nonimmunogenicity, which makes them ideal to deliver different types of drugs, RNAs, and proteins. , These functionalities allow exosomes to be nanotheranostic agents .…”

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.…”

Exosome-transmitted miR-3124-5p promotes cholangiocarcinoma development via targeting GDF11

“…They are broadly distributed in multiple body fluids, such as blood, urine, cerebrospinal fluid, and bile, and have good stability ( 9 ). Accumulating studies have revealed that exosomes play an essential role in cell–cell communication in the tumor microenvironment, and thus contribute to tumorigenesis and development of a variety of cancers ( 10 , 11 ). In addition, exosomes contain a wide range of components, such as proteins, lipids, nucleic acids, mRNAs, and microRNAs (miRNAs), which are clinically important as diagnostic biomarkers, therapeutic targets, and anti-cancer drug delivery vehicles ( 12 ).…”