Abstract

Simple SummaryLung cancer is a leading cause of cancer-related death worldwide and in most cases, detection is usually late and treatment resistance is frequent. For that reason, it is necessary to find biomarkers that could improve the diagnosis and disease management. Exosomes are a type of microvesicles secreted by tumor cells to the medium, with important functions in tumor development. Their analysis can be of utility in diagnosis, including early diagnosis, prognosis, treatment election or follow-up. However, isolation and analysis are cumbersome and can affect the subsequent data information. In this review, we will discuss the recent advances in the role of exosomes in lung cancer and their utility as liquid biopsy, with special attention to isolating methods.Lung cancer is a leading cause of cancer-related death worldwide and in most cases, diagnosis is reached when the tumor has already spread and prognosis is quite poor. For that reason, the research for new biomarkers that could improve early diagnosis and its management is essential. Exosomes are microvesicles actively secreted by cells, especially by tumor cells, hauling molecules that mimic molecules of the producing cells. There are multiple methods for exosome isolation and analysis, although not standardized, and cancer exosomes from biological fluids are especially difficult to study. Exosomes’ cargo proteins, RNA, and DNA participate in the communication between cells, favoring lung cancer development by delivering signals for growth, metastasis, epithelial mesenchymal transition, angiogenesis, immunosuppression and even drug resistance. Exosome analysis can be useful as a type of liquid biopsy in the diagnosis, prognosis and follow-up of lung cancer. In this review, we will discuss recent advances in the role of exosomes in lung cancer and their utility as liquid biopsy, with special attention to isolating methods.

Highlights

  • Exosomes are important players in lung cancer development participating in tumor aggressiveness such as in metastasis, with organ polarization to brain and bone, angiogenesis, immune escape and even drug resistance

  • As the tumor exosomal cargo includes molecules from the releasing cells and can be detected in circulation, exosomes can serve as non-invasive biomarkers providing a potential alternative or at least, a complementary tool to conventional biopsy with additional advantages in the diagnosis, prognosis, therapy election and follow-up

  • Exosome analysis could help in the screening and early detection of lung cancer, when patients have better prognosis [113,124], and some clinical trials are already addressing this issue

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Summary

Exosome Biogenesis and Structure

Cells release several types of microvesicles to the medium that differ in size, cellular origin and cargo: exosomes (50–200 nm), ectosomes (100–1000 nm) and apoptotic bodies (500–5000 nm) [15,16]. Exosome biogenesis initiates with the formation of the multivesicular bodies (MVB) containing many intraluminal vesicles formed by invagination of the endosomal membrane [15,16] (Figure 1) During this process, different materials from the parent cell, such as DNA, mRNAs, microRNAs (miRNAs), non-coding RNAs, lipids and proteins are selectively and actively incorporated into them [17]. Different materials from the parent cell, such as DNA, mRNAs, microRNAs (miRNAs), non-coding RNAs, lipids and proteins are selectively and actively incorporated into them [17] Their release to the medium occurs through the fusion of multivesicular bodies with plasmatic membrane [16]. ExoEsxoomsoemIessohlaatvioenbeaenndobIdtaeinnetidfifcraotmiondifferent biological fluids, such as serum, plasma, urineE,xcoesroembreossphianvael bfleueind oobrtaeixnueddaftreosm[2d7–if3f0e]r.enEtxobsioolmogeicisaollflatuioidns,msuetchhoadss saerreumm,apinllaysma, ubraisneed, ocnertehberior spphiynsaicloflcuheidmoicralepxruodpaetretises[,2s7u–c3h0]a.s sEixzeosoormdeenissiotyl,aotirotnhemirebtihoolodgsicaarlechmara-inly acteristics and molecules expressed in their surface [31,32] These methods differ in effibcaiesnecdy,opnutrhiteyi,r apnhdyesviceonchinemthieciarlcpaproapbielirttyietso, sseulcehct aesxossizoemoersudbepnospituy,laotironthse[i3r3,b3i4o]l.oAgical characteristics and molecules expressed in their surface [31,32].

Method
Exosomes Promote Lung Cancer Angiogenesis
Exosomes Promote Lung Cancer Immune Tolerance
Exosomes as Biomarkers in Lung Cancer
Characterization Methods
Exosomal Proteins
Exosomal miRNAs
Other Nucleic Acids
Findings
Conclusions
Full Text
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