Exosome-related tumor microenvironment

Exosomes are nanoscale phospholipid bilayer vesicles that can be artificially engineered into vectors for the treatment of cancer. Circular RNA (circRNA), a type of non-coding RNA, has crucial regulatory functions in various aspects of cancer, such as tumorigenesis, apoptosis, proliferation, invasion, metastasis and chemo-and radiotherapeutic resistance, as well as in cancer prognosis. Notably, the exosomal transfer of circRNAs may function to both promote and inhibit cancer. Numerous studies have addressed the importance of circRNAs in cancer and non-coding RNAs (such as microRNAs and long non-coding RNAs) in exosomes. However, little research has focussed on a class of RNAs called exosomal circRNAs. The present review discusses current studies regarding exosomal circRNAs, including their biogenesis and biological functions, their abundance in exosomes and possible sorting mechanisms and their potential roles in both promoting and inhibiting cancer. It is predicted that in the next five years there will be increasing research exploring the functional mechanisms of exosomal circRNA in various diseases, in particular their roles in cancer genesis and progression.

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“…4B). (93). The interaction between malignant and surrounding tumour or normal cells can greatly affect tumour progression (94).…”

Section: Exosomes Containing Circrnas Function In Promoting or Inhibimentioning

confidence: 99%

Exosomal circular RNA sorting mechanisms and their function in promoting or inhibiting cancer (Review)

et al. 2020

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“…We previously identified LOXL2 as a candidate factor that could induce pre‐metastatic niche formation in a target lymph node of HNSCC metastasis . Based on the predicted roles of exosomes, which include altering signal transduction between cells and tissues, using exosomes to transport LOXL2 fits well with the concept of exosome‐mediated tumor progression . If LOXL2 is important in establishing pre‐metastatic niche formation, LOXL2 may be dispensable for metastasized tumor cells once premetastatic niches are established; hence, LOXL2 may not be expressed by metastasized tumor cells at metastatic lesions.…”

Section: Discussionmentioning

confidence: 91%

Elevated exosomal lysyl oxidase like 2 is a potential biomarker for head and neck squamous cell carcinoma

et al. 2019

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Objectives: The secretory enzyme lysyl oxidase like 2 (LOXL2) is speculated to contribute to tumor progression through its functions in the remodeling of extracellular matrix and epithelial-mesenchymal transition. We previously identified elevated expression of LOXL2 in metastatic human head and neck squamous cell carcinoma (HNSCC) cells in a mouse lymph node metastases model. Here we performed a case series study examining LOXL2 expression levels in human serum from HNSCC patients to evaluate whether LOXL2 is worth evaluation in a large cohort study.Methods: LOXL2 protein levels in three serum samples from HNSCC patients were assessed by immunoblotting and LOXL2 tissue expression was examined in one human tongue squamous cell carcinoma (SCC) tissue by immunohistochemistry as a representative of HNSCC tissue. Serum samples were further fractionated in exosomes and supernatants by ultracentrifugation, which were then subjected to immunoblot and in vitro LOX activity analyses. Exosomal LOXL2 levels of 36 serum samples from HNSCC patients and seven healthy volunteers were measured using polymer sedimentation exosome preparation followed by ELISA measurement and subjected to statistical analyses.Results: Immunoblot analyses revealed that LOXL2 was present in serum exosomal fractions from three HNSCC patients, and we observed approximately threefold higher levels of LOXL2 in HNSCC patients compared with three healthy volunteers. Immunohistochemical LOXL2 staining was detected in HNSCC cells in addition to non-cancerous lipid tissues and some muscles in human tongue HNSCC tissue. Further measurements of exosomal LOXL2 by ELISA showed over ninefold higher mean LOXL2 levels in patients compared with controls. Statistical analysis revealed a correlation between elevated serum exosomal LOXL2 levels and low-grade, but not high-grade, HNSCC.Conclusions: Our case series study that elevated serum exosomal LOXL2 levels exhibited a correlation with low-grade HNSCCs. A follow-up large cohort clinical study will be required to determine the potential clinical utility of LOXL2 as a new biomarker and/or therapy target for HNSCCs.

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“…Furthermore, different factors are released from cancer cells and stromal cells which can lead to modifications in distant sites, resulting in a favourable scenario for the formation of a pre-metastatic niche [41,42]. Amongst the factors important in this modulation of tumour and stromal cells towards the induction of metastasis and modulation of a oncogenic phenotype, exosomes have been identified ( Figure 2) [43][44][45].…”

Section: Exosomes and Metastasismentioning

confidence: 99%

Exosomes in Bone Sarcomas: Key Players in Metastasis

Chicón-Bosch

Tirado

2020

Cells

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Bone sarcomas are rare cancers which often present with metastatic disease and are still associated with poor survival rates. Studies in the last decade have identified that exosomes, a type of extracellular vesicle released by cells, play an important role in tumour progression and dissemination. Through the transfer of their cargo (RNAs, proteins, and lipids) across cells, they are involved in cellular cross-talk and can induce changes in cellular behaviour. Exosomes have been shown to be important in metastasis organotropism, induction of angiogenesis and vascular permeability, the education of cells towards a pro-metastatic phenotype or the interaction between stromal and tumour cells. Due to the importance exosomes have in disease progression and the high incidence of metastasis in bone sarcomas, recent studies have evaluated the implications of these extracellular vesicles in bone sarcomas. In this review, we discuss the studies that evaluate the role of exosomes in osteosarcoma, Ewing sarcoma, and preliminary data on chondrosarcoma.

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Exosome-related tumor microenvironment

Cited by 61 publications

References 90 publications

Exosomal circular RNA sorting mechanisms and their function in promoting or inhibiting cancer (Review)

Exosomal circular RNA sorting mechanisms and their function in promoting or inhibiting cancer (Review)

Elevated exosomal lysyl oxidase like 2 is a potential biomarker for head and neck squamous cell carcinoma

Exosomes in Bone Sarcomas: Key Players in Metastasis

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