Exosomal Chaperones and miRNAs in Gliomagenesis: State-of-Art and Theranostics Perspectives

Abstract

Gliomas have poor prognosis no matter the treatment applied, remaining an unmet clinical need. As background for a substantial change in this situation, this review will focus on the following points: (i) the steady progress in establishing the role of molecular chaperones in carcinogenesis; (ii) the recent advances in the knowledge of miRNAs in regulating gene expression, including genes involved in carcinogenesis and genes encoding chaperones; and (iii) the findings about exosomes and their cargo released by tumor cells. We would like to trigger a discussion about the involvement of exosomal chaperones and miRNAs in gliomagenesis. Chaperones may be either targets for therapy, due to their tumor-promoting activity, or therapeutic agents, due to their antitumor growth activity. Thus, chaperones may well represent a Janus-faced approach against tumors. This review focuses on extracellular chaperones as part of exosomes’ cargo, because of their potential as a new tool for the diagnosis and management of gliomas. Moreover, since exosomes transport chaperones and miRNAs (the latter possibly related to chaperone gene expression in the recipient cell), and probably deliver their cargo in the recipient cells, a new area of investigation is now open, which is bound to generate significant advances in the understanding and treatment of gliomas.

Curcumin Affects HSP60 Folding Activity and Levels in Neuroblastoma Cells

“…Many investigations have been done in the attempt to use chaperones for the corrections of protein misfolding and treatment of human diseases [41]. Among HSPs, HSP60 has been shown to be involved in brain tumors [1,[42][43][44], and preclinical in vitro and in vivo data have shown that curcumin may be an effective treatment for brain tumors [17]. Nevertheless, it remains to be explored what the effect of curcumin on HSP60 s expression and/or function is.…”

“…The HSP60 secretion is linked to widespread intercellular communication events with various biologic effects. In brain tumors, HSP60 is overexpressed [68,69], and its secretion may be a mechanism involved in cell transformation and in tumor progression, suggesting that HSP60 is a potential therapeutic target for brain tumors treatment [42].…”

Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma

“…The intravesicular cargo may variate depending on the cell type that secretes them and according to their specific function on the recipient cell, such as cytokines [95], hormones [96], transcription factors, growth factors [97] and heat shock proteins [98][99][100][101][102][103][104][105][106][107]. Moreover, there is a large number of proteins that compose the structure of exosomes, which are directly involved in cell trafficking and their specificity: exosomes are enriched in proteins involved in the vesicles' trafficking, cell surface receptors such as tumor susceptibility gene 101 (TSG101); integrin and a number of tetraspanins such as CD9, CD53, CD63, CD81 and CD82 [108,109].…”

Extracellular Vesicles in Glioma: From Diagnosis to Therapy

“…HSPs have been reported to be a constant cargo feature of exosomes and other EVs. Hence, glioma cell‐derived EVs (especially exosomes) harboring an abundance of HSPs have a high potential for use in diagnostic purposes …”