Exosomes in cancer development, metastasis, and immunity.
Zhang Lin,Yu Dihua
Biochimica et biophysica acta. Reviews on cancer
Exosomes play essential roles in intercellular communications. The exosome was discovered in 1983, when it was found that reticulocytes release 50-nm small vesicles carrying transferrin receptors into the extracellular space. Since then, our understanding of the mechanism and function of the exosome has expanded exponentially that has transformed our perspective of inter-cellular exchanges and the molecular mechanisms that underlie disease progression. Cancer cells generally produce more exosomes than normal cells, and exosomes derived from cancer cells have a strong capacity to modify both local and distant microenvironments. In this review, we summarize the functions of exosomes in cancer development, metastasis, and anti-tumor or pro-tumor immunity, plus their application in cancer treatment and diagnosis/prognosis. Although the exosome field has rapidly advanced, we still do not fully understand the regulation and function of exosomes in detail and still face many challenges in their clinical application. Continued discoveries in this field will bring novel insights on intercellular communications involved in various biological functions and disease progression, thus empowering us to effectively tackle accompanying clinical challenges.
Plasma exosomes as novel biomarker for the early diagnosis of gastric cancer.
Wang Jianjun,Liu Yuanyuan,Sun Wangwei,Zhang Qinghui,Gu Tao,Li Guangxin
Cancer biomarkers : section A of Disease markers
Exosomes are lipid bilayer vesicles of endocytic origin ranging from 30 to 100 nm in size, and contain various nucleic acid molecules such as DNA, mRNA, miRNA, lncRNA and multiple proteins, which could be transferred into target cells. Recent study indicated that exosomes as information carriers between cells has introduced us to a new previously unknown biological communication system. Increasing evidences show that exosomes play a crucial role in gastric cancer because they are potential to influence normal cellular physiology and promote various states of the cancer. In this review, we focus on the latest findings on exosomes in the plasma of gastric cancer patients, mainly summarizing the functions of miRNAs, lncRNAs and multiple proteins in diagnosis, prognosis, and in establishing treatment regimens against gastric cancer. Furtherly, potential functions of exosomes as novel diagnostic biomarkers for gastric cancer are discussed extensively. Exosomes are believed to be a non-invasive disease biomarker with a dual capability to provide insights into the early diagnosis for gastric cancer.
Tumor exosomes: a double-edged sword in cancer therapy.
Sun Wei,Luo Ju-Dong,Jiang Hua,Duan Dayue Darrel
Acta pharmacologica Sinica
Tumor cells produce and secrete more nucleic acids, proteins and lipids than normal cells. These molecules are transported in the blood or around the cells in membrane-encapsulated exosomes. Tumor-derived or tumor-associated exosomes (usually 30-100 nm in diameter) contain abundant biological contents resembling those of the parent cells along with signaling messengers for intercellular communication involved in the pathogenesis, development, progression, and metastasis of cancer. As these exosomes can be detected and isolated from various body fluids, they have become attractive new biomarkers for the diagnosis and prognosis of cancer. Furthermore, tumor exosomes have also attracted increasing attention due to their potential as novel therapeutic strategies for the treatment of cancers. On the one hand, the lipid bilayer membrane-encapsulated vesicles are promising carriers of drugs and other therapeutic materials targeting specific cancer cells. On the other hand, tumor exosomes are important mediators for modulation of the microenvironment that orchestrates events critical to the growth and metastasis of cancer cells as well as chemoresistance. Here, we summarize the advances in our understanding of tumor-associated or tumor-derived exosomes in recent years, and discuss their roles in cancer development, progression, invasion, and metastasis of cancers and, more importantly, their potential in strategies for precision therapy of various cancers as well as important caveats.
Exosomes in cancer: Small transporters with big functions.
Li Xi,Wang Yanan,Wang Qi,Liu Yinping,Bao Wei,Wu Sufang
Exosomes are nanosized membrane-bound vesicles containing abundant proteins, DNA, mRNA, and non-coding RNAs. Exosomes are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material. Increasing studies have shown that exosomes play an important role in tumour initiation, growth, progression, metastasis, drug resistance and immune escape. In this article, we review recent advances in the biology of exosomes. We elaborate the specific mechanism by which exosomes affect the communication between tumours and the microenvironment. Finally, we report that exosomes may provide promising biomarkers for cancer diagnosis and represent new targets for cancer therapy.
Implications of exosomes as diagnostic and therapeutic strategies in cancer.
Aghebati-Maleki Ali,Nami Sanam,Baghbanzadeh Amir,Karzar Bita H,Noorolyai Saeed,Fotouhi Ali,Aghebati-Maleki Leili
Journal of cellular physiology
Exosomes offer a new perspective on the biology of cancer with both diagnostic and therapeutic concepts. Due to the cell-to-cell association, exosomes are involved in the progression, metastasis, and therapeutic efficacy of the tumor. They can be isolated from blood and other body fluids to determine the disease progression in the body, including cancer growth. In addition to being reservoirs of biochemical markers of cancer, exomes can be designed to restore tumor immunity. Tumor exosomes interact with different cells in the tumor microenvironment to confer beneficial modulations, responsible for stromal activity, angiogenesis, increased vascular permeability, and immune evasion. Exosomes also contribute to the metastasis with the aim of epithelial transmission to the mesenchyme and the formation of premetastatic niches. Moreover, exosomes protect cells against the cytotoxic effects of chemotherapeutic drugs and prevent the transmission of chemotherapy resistance to adjacent cells. Therefore, exosomes are essential for many fatal cancer agents, and understanding their origins and role in cancer is important. In this article, we attempted to clarify the potential of exosomes for the application in cancer diagnosis and therapy.
Pegtel D Michiel,Gould Stephen J
Annual review of biochemistry
Exosomes are small, single-membrane, secreted organelles of ∼30 to ∼200 nm in diameter that have the same topology as the cell and are enriched in selected proteins, lipids, nucleic acids, and glycoconjugates. Exosomes contain an array of membrane-associated, high-order oligomeric protein complexes, display pronounced molecular heterogeneity, and are created by budding at both plasma and endosome membranes. Exosome biogenesis is a mechanism of protein quality control, and once released, exosomes have activities as diverse as remodeling the extracellular matrix and transmitting signals and molecules to other cells. This pathway of intercellular vesicle traffic plays important roles in many aspects of human health and disease, including development, immunity, tissue homeostasis, cancer, and neurodegenerative diseases. In addition, viruses co-opt exosome biogenesis pathways both for assembling infectious particles and for establishing host permissiveness. On the basis of these and other properties, exosomes are being developed as therapeutic agents in multiple disease models.
Exosomes and their role in tumorigenesis and anticancer drug resistance.
Milman Neta,Ginini Lana,Gil Ziv
Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy
Exosomes are a class of extracellular vesicles ranging in size from 40 to 100 nm, which are secreted by both cancer cells and multiple stromal cells in the tumor microenvironment. Following their secretion, exosomes partake in endocrine, paracrine and autocrine signaling. Internalization of exosomes by tumor cells influences several cellular pathways which alter cancer cell physiology. Tumor-derived exosomes secreted by cancer or stromal cells can also confer anticancer drug-resistant traits upon cancer cells. These exosomes promote chemoresistance by transferring their cargo which includes nucleic acids, proteins, and metabolites to cancer cells or act as a decoy for immunotherapeutic targets. Depletion of exosomes can reverse some of the detrimental effects on tumor metabolism and restore drug sensitivity to chemotherapeutic treatment. Herein we discuss various approaches that have been developed to deplete exosomes for therapeutic purposes. The natural composition, low immunogenicity and cytotoxicity of exosomes, along with their ability to specifically target tumor cells, render them an appealing platform for drug delivery. The ability of exosomes to mediate autocrine and paracrine signaling in target cells, along with their natural structure and low immunogenicity render them an attractive vehicle for the delivery of anticancer drugs to tumors.