MassIVE MSV000098313

Partial Public PXD065421

Extracellular vesicles derived from tumor-associated macrophages reveal unique contributions to the ovarian cancer microenvironment

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Description

Tumor progression and metastasis are promoted by ascites which constitutes a central part of the ovarian cancer (OC) tumor microenvironment (TME). One prominent immune cell type in ascites is represented by tumor-associated macrophages (TAMs) which contribute to tumor progression. Among other cells, ascites is highly enriched in soluble factors, as well as extracellular vesicles (EVs). It remains relatively unknown, how far TAMs contribute to the EV compartment of the TME. In this work, peripheral blood monocytes from healthy donors were differentiated into monocyte-derived macrophages (MDMs) and polarized into classically activated (M1-like), alternatively activated (M2-like) and TAM-like (by ascites incubation). For all subtypes, serum-free conditioned medium was collected in for 24h and EVs were isolated and characterized by nano-flow cytometry (nFC), label-free mass spectrometry and electron microscopy, among others. Our results demonstrated distinct traits for EV release and cargo across different macrophage subtypes. Particularly, TAM-like MDMs displayed a handicapped small EV release, supported by a total low particle concentration with low frequency of tetraspanin-positive events. These EV subpopulations displayed sizing profiles closer to M1-like than M2-like particles. Also, the low particle release in these cells was supported by truncated expression of EV biogenesis markers (i.e., FLOT-1, TSG101) and a decreased N-glycosylation of CD63 protein in TAM-like MDMs, which was validated in patient-derived samples. Remarkably, the EV-associated proteome of TAMs, displayed significant enrichment in both pro- and anti-inflammatory molecules with clinical value. Interestingly, markers significantly enriched in the ascites TAM-EV signature were mostly associated with poor prognosis, whereas M1-like EV-related markers (pro-inflammatory) were mostly associated with longer survival. Finally, our results confirmed previous data for CD163 and MRC1 to be associated to TAM-EVs, while also describing novel EV-associated candidates to present both diagnostic (i.e., COLEC12) and prognostic (i.e., MRS1) value at circulating levels. Taken together, our data support a unique secretory profile of TAMs in OC providing new biomarkers with translational impact. As for the particularly low particle release, the biogenesis routes involved and the mechanisms behind TAM-EV function need to be further investigated to gain a better understanding of the participation of these cells in the TME landscape. [doi:10.25345/C50V89W2H] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: dia ; Dia-NN ; Exploris ; autonomics ; EV ; Extracellular vesicles ; ovarian cancer microenvironment ; macrophages ; nano-flow cytometry ; DatasetType:Proteomics

Contact

Principal Investigators:
(in alphabetical order) 		Maria Gomez-Serrano, Center for Tumor Biology and Immunology, Philipps University, 35043 Marburg, Germany
Submitting User: Wszymanski

Publications

Pörschke J, Heidemann S, Nehring HP, Lluch A, Szyma?ski W, Finkernagel F, Preußer C, Bhagwat AM, Stamm TJ, Sommerfeld L, Helmprobst F, Müller R, Reinartz S, Graumann J, Pogge von Strandmann E, Gómez-Serrano M.
Tumor-associated macrophages display differential protein cargo sorting in extracellular vesicles associated with poor survival in ovarian cancer.
Mol Med. Epub 2026 Jan 30.

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