Cancer Stem Cell-Exosomes, Unexposed Player in Tumorigenicity (original) (raw)

Exosomes: Definition, Role in Tumor Development and Clinical Implications

Cancer Microenvironment, 2018

Exosomes are microvesicles released by cells in both physiological and pathological situations. They are surrounded by a lipid bilayer with proteins derived from the origin cell, and contain a variety of molecules, such as nucleic acids. They represent an emerging mechanism of intercellular communication, and they play an important role in the pathogenesis of cancer, stimulating proliferation and aggressiveness of cancer cells, inducing a microenvironment favorable to tumor development and controlling immune responses. Because of the growing understanding of the potential implications of extracellular vesicles in the development of malignancies, research on exosomes, and its role as a diagnostic and therapeutic tool, constitutes nowadays a very exciting and promising field.

Expanding on Exosomes and Ectosomes in Cancer

New England Journal of Medicine, 2015

Exosomes are tiny vesicles that are enriched in nucleic acids and proteins and released from cells. Originally considered to have no biologic significance, these nano-sized blebs are now considered to be mini-maps of their cells of origin, with physiological and pathologic relevance. In cancer, they have been implicated in the muddling of cell-to-cell communication and in the transfer of "undesirable" information from one cell to another. Consequences include stimulating the proliferation, motility, and invasive properties of the recipient cell, transferring drug resistance, inducing the formation of endothelial tubules (e.g., in angiogenesis), and attracting cancer cells to secondary sites within living organisms. That said, our understanding of exosomes is rudimentary.

Exosomes, cancer’s little army

Stem Cell Investigation, 2019

In an attempt to conceptualize the process of cancer formation, Hanahan and Weinberg [2000] have outlined six universal characteristics of tumorigenesis, and labelled them as the "hallmarks of cancer". These hallmarks include; unlimited proliferation, evading growth suppressors, resisting cell death, replicative immortality, inducing angiogenesis, initiating invasion and metastasis. Cancer cell signalling is crucial for initiating and controlling cellular pathways that are involved in these hallmarks. The intricate network of communication between cancer cells and other cancer or non-cancer cells is still being investigated, and is yet to be fully understood. Initially it was proposed that the main form of communication between cells within the tumour microenvironment are soluble growth factors, and gap junctions. Then, researchers reported another form of cell-to-cell communication, through the release of spherical particles called exosomes. It is believed that these exosomes enable communication through the transfer of active components from the releasing cell, and off-loading it into the recipient cell. As researchers continue to examine the development of the cancer hallmarks and the pathways involved, it became evident that cancer cell-derived exosomes play a major role in almost all of them. This review will examine the role played by cancer cell-derived exosomes in development of cancer.

Tumorigenic and tumoricidal properties of exosomes in cancers; a forward look

Cell communication and signaling, 2024

In recent decades, emerging data have highlighted the critical role of extracellular vesicles (EVs), especially (exosomes) Exos, in the progression and development of several cancer types. These nano-sized vesicles are released by different cell lineages within the cancer niche and maintain a suitable platform for the interchange of various signaling molecules in a paracrine manner. Based on several studies, Exos can transfer oncogenic factors to other cells, and alter the activity of immune cells, and tumor microenvironment, leading to the expansion of tumor cells and metastasis to the remote sites. It has been indicated that the cell-to-cell crosstalk is so complicated and a wide array of factors are involved in this process. How and by which mechanisms Exos can regulate the behavior of tumor cells and non-cancer cells is at the center of debate. Here, we scrutinize the molecular mechanisms involved in the oncogenic behavior of Exos released by different cell lineages of tumor parenchyma. Besides, tumoricidal properties of Exos from various stem cell (SC) types are discussed in detail.

The Role of Exosomes in Cancer Progression

International Journal of Molecular Sciences

Early detection, characterization and monitoring of cancer are possible by using extracellular vesicles (EVs) isolated from non-invasively obtained liquid biopsy samples. They play a role in intercellular communication contributing to cell growth, differentiation and survival, thereby affecting the formation of tumor microenvironments and causing metastases. EVs were discovered more than seventy years ago. They have been tested recently as tools of drug delivery to treat cancer. Here we give a brief review on extracellular vesicles, exosomes, microvesicles and apoptotic bodies. Exosomes play an important role by carrying extracellular nucleic acids (DNA, RNA) in cell-to-cell communication causing tumor and metastasis development. We discuss the role of extracellular vesicles in the pathogenesis of cancer and their practical application in the early diagnosis, follow up, and next-generation treatment of cancer patients.

Composition, Biogenesis, and Role of Exosomes in Tumor Development

Stem Cells International

The role of exosomes and their mechanism of action at the tumor site have received increasing attention. These microvesicles are produced by a wide range of cells including mesenchymal stem cells (MSCs) and immune cells. In particular, tumor cells release remarkable amounts of exosomes which spread to distant organs through the blood and enhance the possibility of tumor metastasis. In spite of results on tumor promoting properties, there are reports demonstrating the tumor inhibiting effects of exosomes depending on the type of the tumor and cell source. This review aims to have a comprehensive appraisal on the biogenesis, composition, and isolation of exosomes and then highlights the current knowledge of their role in cancer progression or inhibition by special focusing on MSC’s exosomes (MSC-EXOs).

Exosomes: key players in cancer and potential therapeutic strategy

Signal Transduction and Targeted Therapy, 2020

Exosomes are extracellular vesicles secreted by most eukaryotic cells and participate in intercellular communication. The components of exosomes, including proteins, DNA, mRNA, microRNA, long noncoding RNA, circular RNA, etc., which play a crucial role in regulating tumor growth, metastasis, and angiogenesis in the process of cancer development, and can be used as a prognostic marker and/or grading basis for tumor patients. Hereby, we mainly summarized as followed: the role of exosome contents in cancer, focusing on proteins and noncoding RNA; the interaction between exosomes and tumor microenvironment; the mechanisms that epithelial-mesenchymal transition, invasion and migration of tumor affected by exosomes; and tumor suppression strategies based on exosomes. Finally, the application potential of exosomes in clinical tumor diagnosis and therapy is prospected, which providing theoretical supports for using exosomes to serve precise tumor treatment in the clinic.

Exosomes: a potential diagnostic and treatment modality in the quest for counteracting cancer

Cellular Oncology

Background Exosomes are nanosized bio vesicles formed when multivesicular bodies and the plasma membrane merge and discharge into bodily fluids. They are well recognized for facilitating intercellular communication by transporting numerous biomolecules, including DNA, RNAs, proteins, and lipids, and have been implicated in varied diseases including cancer. Exosomes may be altered to transport a variety of therapeutic payloads, including as short interfering RNAs, antisense oligonucleotides, chemotherapeutic drugs, and immunological modulators, and can be directed to a specific target. Exosomes also possess the potential to act as a diagnostic biomarker in cancer, in addition to their therapeutic potential. Conclusion In this review, the physiological roles played by exosomes were summarized along with their biogenesis process. Different isolation techniques of exosomes including centrifugation-based, size-based, and polymer precipitation-based techniques have also been described in detail with a special focus on cancer therapeutic applications. The review also shed light on techniques of incubation of drugs with exosomes and their characterization methods covering the most advanced techniques. Myriad applications of exosomes in cancer as diagnostic biomarkers, drug delivery carriers, and chemoresistancerelated issues have been discussed at length. Furthermore, a brief overview of exosome-based anti-cancer vaccines and a few prominent challenges concerning exosomal delivery have been concluded at the end. Keywords Exosomes • cancer • Biomarkers • Isolation • Biogenesis Abbreviations ABCA-3 ATP binding cassette transporter-A3 ABCG-2 ATP binding cassette transporter-G2 AFM Atomic force microscopy AHSG Alpha-2-HS-glycoprotein CA-125 Cancer antigen-125 CAS-9 CRISPR associated protein 9 CIB1 Cryptochrome interacting basic helix-loop-helix1 CLIC/GEEC CDC-42 dependent clathrin-independent carrier /GPI-APenriched compartment