scholarly journals Extracellular Vesicles and Carried miRNAs in the Progression of Renal Cell Carcinoma

2019 ◽  
Vol 20 (8) ◽  
pp. 1832 ◽  
Author(s):  
Cristina Grange ◽  
Alessia Brossa ◽  
Benedetta Bussolati

The formation and maintenance of renal cell carcinomas (RCC) involve many cell types, such as cancer stem and differentiated cells, endothelial cells, fibroblasts and immune cells. These all contribute to the creation of a favorable tumor microenvironment to promote tumor growth and metastasis. Extracellular vesicles (EVs) are considered to be efficient messengers that facilitate the exchange of information within the different tumor cell types. Indeed, tumor EVs display features of their originating cells and force recipient cells towards a pro-tumorigenic phenotype. This review summarizes the recent knowledge related to the biological role of EVs, shed by renal tumor cells and renal cancer stem cells in different aspects of RCC progression, such as angiogenesis, immune escape and tumor growth. Moreover, a specific role for renal cancer stem cell derived EVs is described in the formation of the pre-metastatic niche. We also highlight the tumor EV cargo, especially the oncogenic miRNAs, which are involved in these processes. Finally, the circulating miRNAs appear to be a promising source of biomarkers in RCC.

Endocrinology ◽  
2021 ◽  
Author(s):  
Amy E Baek ◽  
Natalia Krawczynska ◽  
Anasuya Das Gupta ◽  
Svyatoslav Victorovich Dvoretskiy ◽  
Sixian You ◽  
...  

Abstract Cholesterol has been implicated in the clinical progression of breast cancer, a disease that continues to be the most commonly diagnosed cancer in women. Previous work has identified the cholesterol metabolite, 27-hydroxycholesterol (27HC), as a major mediator of the effects of cholesterol on breast tumor growth and progression. 27HC can act as an estrogen receptor (ER) modulator to promote the growth of ERα+ tumors, and a liver x receptor (LXR) ligand in myeloid immune cells to establish an immune-suppressive program. In fact, the metastatic properties of 27HC require the presence of myeloid cells, with neutrophils (PMNs) being essential for the increase in lung metastasis in murine models. In an effort to further elucidate the mechanisms by which 27HC alters breast cancer progression, we made the striking finding that 27HC promoted the secretion of extracellular vesicles (EVs), a diverse assortment of membrane bound particles that include exosomes. The resulting EVs had a size distribution that was skewed slightly larger, compared to EVs generated by treating cells with vehicle. The increase in EV secretion and size was consistent across three different subtypes: primary murine PMNs, RAW264.7 monocytic cells and 4T1 murine mammary cancer cells. Label-free analysis of 27HC-EVs indicated that they had a different metabolite composition to those from vehicle-treated cells. Importantly, 27HC-EVs from primary PMNs promoted tumor growth and metastasis in two different syngeneic models, demonstrating the potential role of 27HC induced EVs in the progression of breast cancer. EVs from PMNs were taken up by cancer cells, macrophages and PMNs, but not T cells. Since EVs did not alter proliferation of cancer cells, it is likely that their pro-tumor effects are mediated through interactions with myeloid cells. Interestingly, RNA-seq analysis of tumors from 27HC-EV treated mice do not display significantly altered transcriptomes, suggesting that the effects of 27HC-EVs occur early on in tumor establishment and growth. Future work will be required to elucidate the mechanisms by which 27HC increases EV secretion, and how these EVs promote breast cancer progression. Collectively however, our data indicate that EV secretion and content can be regulated by a cholesterol metabolite, which may have detrimental effects in terms of disease progression, important findings given the prevalence of both breast cancer and hypercholesterolemia.


2019 ◽  
Vol 20 (13) ◽  
pp. 3236 ◽  
Author(s):  
Michela Colombo ◽  
Domenica Giannandrea ◽  
Elena Lesma ◽  
Andrea Basile ◽  
Raffaella Chiaramonte

Extracellular vesicles (EVs) represent a heterogeneous group of membranous structures shed by all kinds of cell types, which are released into the surrounding microenvironment or spread to distant sites through the circulation. Therefore, EVs are key mediators of the communication between tumor cells and the surrounding microenvironment or the distant premetastatic niche due to their ability to transport lipids, transcription factors, mRNAs, non-coding regulatory RNAs, and proteins. Multiple myeloma (MM) is a hematological neoplasm that mostly relies on the bone marrow (BM). The BM represents a highly supportive niche for myeloma establishment and diffusion during the formation of distant bone lesions typical of this disease. This review represents a survey of the most recent evidence published on the role played by EVs in supporting MM cells during the multiple steps of metastasis, including travel and uptake at distant premetastatic niches, MM cell engraftment as micrometastasis, and expansion to macrometastasis thanks to EV-induced angiogenesis, release of angiocrine factors, activation of osteolytic activity, and mesenchymal cell support. Finally, we illustrate the first evidence concerning the dual effect of MM-EVs in promoting both anti-tumor immunity and MM immune escape, and the possible modulation operated by pharmacological treatments.


2020 ◽  
Vol 147 (6) ◽  
pp. 1694-1706 ◽  
Author(s):  
Alessia Brossa ◽  
Valentina Fonsato ◽  
Cristina Grange ◽  
Stefania Tritta ◽  
Marta Tapparo ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1400 ◽  
Author(s):  
Manuel Castanheira de Oliveira ◽  
Hugo R. Caires ◽  
Maria J. Oliveira ◽  
Avelino Fraga ◽  
M. Helena Vasconcelos ◽  
...  

Extracellular vesicles (EVs) are small membrane vesicles released by all cells and involved in intercellular communication. Importantly, EVs cargo includes nucleic acids, lipids, and proteins constantly transferred between different cell types, contributing to autocrine and paracrine signaling. In recent years, they have been shown to play vital roles, not only in normal biological functions, but also in pathological conditions, such as cancer. In the multistep process of cancer progression, EVs act at different levels, from stimulation of neoplastic transformation, proliferation, promotion of angiogenesis, migration, invasion, and formation of metastatic niches in distant organs, to immune escape and therapy resistance. Moreover, as products of their parental cells, reflecting their genetic signatures and phenotypes, EVs hold great promise as diagnostic and prognostic biomarkers. Importantly, their potential to overcome the current limitations or the present diagnostic procedures has created interest in bladder cancer (BCa). Indeed, cystoscopy is an invasive and costly technique, whereas cytology has poor sensitivity for early staged and low-grade disease. Several urine-based biomarkers for BCa were found to overcome these limitations. Here, we review their potential advantages and downfalls. In addition, recent literature on the potential of EVs to improve BCa management was reviewed and discussed.


2013 ◽  
Vol 11 (11) ◽  
pp. 1375-1386 ◽  
Author(s):  
Hye Won Lee ◽  
Kyeung Min Joo ◽  
Joung Eun Lim ◽  
Hyun Jung Cho ◽  
Hee Jin Cho ◽  
...  

2012 ◽  
Vol 72 (8) ◽  
pp. 1953-1963 ◽  
Author(s):  
Sònia Tugues ◽  
Satoshi Honjo ◽  
Christian König ◽  
Oriol Noguer ◽  
Marie Hedlund ◽  
...  

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