Dissecting the multi-omics atlas of the exosomes released by human lung adenocarcinoma stem-like cells

Abstract

Lung adenocarcinoma is heterogeneous and hierarchically organized, with a subpopulation of stem-like cells (CSCs) that reside at the apex of the hierarchy, in which exosomes act as important mediators by transporting specific molecules among different cell populations. Although there have been numerous studies on tumor exosomes, the constituents and functional properties of CSC-derived exosomes are still poorly characterized. Here we present a detail transcriptome and proteome atlas of the exosomes released by human lung adenocarcinoma stem-like cells (LSLCs). The transcriptome analysis indicates the specific patterns of exosomal constituents, including the fragmentation of transcripts and the low-level presence of circular RNAs, and identifies multiple exosomal-enriched mRNAs and lncRNAs. Integrative analysis of transcriptome and proteome data reveals the diverse functions of exosomal-enriched RNAs and proteins, many of which are associated with tumorigenesis. Importantly, several LSLC markers we identified are highly expressed in LSLC-derived exosomes and associate with poor survival, which may serve as promising liquid biopsy biomarkers for lung adenocarcinoma diagnosis. Our study provides a resource for the future elucidation of the functions of tumor-derived exosomes and their regulatory mechanisms in mediating lung cancer development.

Identification of Novel Multi-Omics Expression Landscapes and Meta-Analysis of Landscape-Based Competitive Endogenous RNA Networks in ALDH+ Lung Adenocarcinoma Stem Cells

“…Increasing research has demonstrated that the leading cause of poor prognosis for LUAD [7] is the presence of LUAD stem cells [8], which could initiate and sustain primary and metastatic cancer relapse and growth [9]. Previous evidence [10] and our most recent studies [11,12] showed that ALDH+ H1975 LUAD cells (LSCs) display strong CSC-like properties [13] and act as LSCs to influence the formation of a tumor niche, tumor initiation, and recurrence [7]. Our most recent study revealed that LSCs have the capacity for self-renewal and differentiation, which facilitates the generation of tumor cells and promotes tumor growth [11], recurrence, and metastasis.…”

Cancer Stem Cells and Their Vesicles, Together with Other Stem and Non-Stem Cells, Govern Critical Cancer Processes: Perspectives for Medical Development

“…Most often, however, they can be envisaged according to general criteria. CSCs share some properties with MSCs, including broad proliferation and activation of various signaling processes [ 18 , 19 , 20 , 34 ]. Relevant to CSCs are the cellular cross-talks also involving, together with stem cells, non-cancer cells accumulated at the niches [ 15 , 16 , 24 , 25 , 35 ] ( Table 1 ; Figure 1 ).…”

“…However, most key properties of CSCs are specific [ 17 , 34 ]; their modulation appears largely focused on self-renewal and multi-lineage differentiations [ 20 , 21 ], which is different from those of the MSC family. CSCs show multi-lineage properties, leading to the generation of distinct cancer subtypes [ 18 , 21 ]. Moreover, CSCs participate in many critical processes of cancer, from initiation and progression to formation of metastases, therapy resistance, and cancer relapse ( Table 1 ) [ 17 , 21 , 22 , 23 ].…”

“…More recent studies, which started approximately two decades after CSC identification, led to functional and pathological characterization of CSCs cells. Small populations of heterogeneous CSCs revealed their capacity for self-renewal and aberrant differentiation to be specific for immortality and divergent lineages of cancer cells [ 18 ]. In cancer tissue CSC concentrations occur within small volumes, the niches, analogous to the stromas of non-cancer cells [ 19 ].…”

Emerging function and clinical significance of extracellular vesicle noncoding RNAs in lung cancer

“…For instance, Luo et al. 235 reported the transcriptomics and proteomics landscape of EVs derived from human LAC stem-like cells. They obtained a variety of mRNAs, circRNAs, and lncRNAs enriched in EVs through transcriptomics analysis.…”