title: Qualitative changes in the proteome of extracellular vesicles accompanying cancer cell transition to mesenchymal state.
abstract: Transitions of the cancer cell phenotype between epithelial and mesenchymal states (EMT) are likely to alter the patterns of intercellular communication. In this regard we have previously documented that EMT-like changes trigger quantitative rearrangements in exosomal vesicle emission in A431 cancer cells driven by oncogenic epidermal growth factor receptor (EGFR). Here we report that extracellular vesicles (EVs) produced by these cancer cells in their epithelial and mesenchymal states exhibit profound qualitative differences in their proteome. Thus, induction of the EMT-like state through blockade of E-cadherin and EGFR stimulation provoked a mesenchymal shift in cellular morphology and enrichment in the CD44-high/CD24-low immunophenotype, often linked to cellular stemness. This change also resulted in reprogramming of the EV-related proteome (distinct from that of corresponding cells), which contained 30 unique protein signals, and revealed enrichment in pathways related to cellular growth, cell-to-cell signaling, and cell movement. Some of the most prominent EV-related proteins were validated, including integrin α2 and tetraspanin CD9. We propose that changes in cellular differentiation status translate into unique qualitative rearrangements in the cargo of EVs, a process that may have implications for intercellular communication and could serve as source of new biomarkers to detect EMT-like processes in cancer.
authors: Montreal Children's Hospital, RI MUHC, McGill University, Montreal, Quebec, Canada.
authors: Delphine
authors: D
authors: Garnier
authors: Nathalie
authors: N
authors: Magnus
authors: Brian
authors: B
authors: Meehan
authors: Thomas
authors: T
authors: Kislinger
authors: Janusz
authors: J
authors: Rak
mesh_terms: D051927:CD24 Antigen / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D065150:Cellular Reprogramming; D058750:Epithelial-Mesenchymal Transition; D055354:Exosomes / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D039421:Integrin alpha2 / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism; D020543:Proteome / Q000235:genetics* / Q000378:metabolism; D060245:Tetraspanin 29 / Q000235:genetics / Q000378:metabolism
chemical_list: D051927:CD24 Antigen; D015820:Cadherins; D018960:Hyaluronan Receptors; D039421:Integrin alpha2; D020543:Proteome; D060245:Tetraspanin 29
keywords: Cancer; Cancer stem cells; E-cadherin; EGFR; EMT; EVs; Epidermal Growth Factor Receptor; Epithelial-to-Mesenchymal Transition; Exosomes; Extracellular Vesicles; Extracellular vesicles; Oncogenes; Proteome; TGFα; Transforming Growth Factor alpha