Exosomes in hepatocellular carcinoma: a new horizon

Abstract

Exosomes are a class of extracellular vesicles released by multiple cells types including tumor cells, with a size range of 30-100 nm and a lipid bilayer membrane. Recently, the role of exosomes in cell-to-cell communication has been extensively studied, showed that exosomes can deliver their functional RNAs and proteins to recipient cells, impacting transcription and translation of recipient cells. Emerging evidence suggests that hepatocellular carcinoma (HCC) cell-derived exosomes can construct a fertile environment to support HCC cells proliferation, grow, invasion and metastasis, development of drug resistance. Circulating exosomes can be used as noninvasive biomarkers for early diagnosis, moreover as drug delivery vehicles, provide new insights into the treatment of HCC.

EVs as Potential New Therapeutic Tool/Target in Gastrointestinal Cancer and HCC

“…Collectively, these data support the idea that small EVs are the most commonly researched among all EVs in HCC [ 103 , 104 , 105 ]. Notwithstanding, the relationship between large EVs and HCC has been recently considered.…”

The significance of exosomes in the development and treatment of hepatocellular carcinoma

“…Increasing evidence reveals that exosomes could participate in the growth and metastasis of HCC, such as by secreting miRNAs or other substances by regulating the growth and metastasis of HCC. The major reason for difficult treatment and poor prognosis is due to intrahepatic and distal metastasis [4], and so it is imperative to make clear the detailed mechanism of HCC. HCC cells secrete miRNA-21, resulting in the activation of PDK1/ AKT signaling in HSCs.…”

“…Hepatocellular carcinoma (HCC) is the third most common malignancy in the world, accounting for 85-90% of primary liver cancer [1][2][3]. The annual incidence of new cases with HCC is estimated to be about 841,000 [4]. Hepatitis B virus (HBV) infection is considered as the main risk factor for HCC development in China [5].…”

“…Exosomes are small nano-sized vesicles that transport biologically active molecules between cells, regulate microenvironment and immune system between cells by a variety of biomolecules (such as proteins, RNA and DNA) [4,12,13], and the genetic and epigenetic mechanisms of cells [14]. Studies have shown that exosomes not only initiates the downstream signals to target cells, but also transfers the genetic material to downstream cells, providing intercellular communication with a new mechanism [4]. It has been reported that different types of exosomal compositions provided by databases such as Vesiclepedia, EVpedia, and Exocarta were found in different cells with similar physiological or pathological conditions [15][16][17].…”

The functional role of surface molecules on extracellular vesicles in cancer, autoimmune diseases, and coagulopathy

“…One study has attempted generating exosomes displaying carcinoembryonic antigen and Her2 and found an enhanced T-and B-cell response in animals vaccinated with these exosomes, suggesting that recombinant EVs may be materials for antitumor vaccines by presenting desired antigens on their surface. 74 Another study has attempted to use exosomes derived from T cells delivery. 95 The system using surface Lamp2b as part of the delivery platform can potentially be modified to target any population of tumor cells by associating a specific ligand to Lamp2b and loading a desired drug into the Lamp2b expressing EVs; for example, delivering imatinib to IL3 receptor-overexpressing chronic myeloid leukemia cells by engineering Lamp2b-IL3 expressing EVs.…”