Lipid droplets and small extracellular vesicles: More than two independent entities
Despite increasing knowledge about small extracellular vesicle (sEV) composition and functions in cell-cell communication, the mechanism behind their biogenesis remains unclear. Here, we reveal for the first time that sEV biogenesis and release into the microenvironment are tightly connected with another important organelle, Lipid Droplets (LDs). The correlation was observed in several human cancer cell lines as well as patient-derived colorectal cancer stem cells (CR-CSCs). Our results demonstrated that external stimuli such as radiation, pH, hypoxia or lipid-interfering drugs, known to affect the number of LDs/cell, similarly influenced sEV secretion. Importantly, through multiple omics data, at both mRNA and protein levels, we revealed RAB5C as a potential important molecular player behind this organelle connection. Altogether, the potential to fine-tune sEV biogenesis by targeting LDs could significantly impact the amount, cargos and properties of these sEVs, opening new clinical perspectives.
Authors
- Joao Seco (ORCID: https://orcid.org/0000-0002-9458-2202)
- Simone Di Franco (ORCID: https://orcid.org/0000-0002-6217-2161)
- Daniel García-Calderón (ORCID: https://orcid.org/0000-0003-3322-8004)
- Francesca Pagliari (ORCID: https://orcid.org/0000-0002-5547-222X)
- Francesco Costanzo (ORCID: https://orcid.org/0000-0002-3096-9416)
- Rachel Hanley (ORCID: https://orcid.org/0000-0002-2627-1146)
- Michelle Neßling (ORCID: https://orcid.org/0000-0002-0663-4026)
- Carlo Liberale (ORCID: https://orcid.org/0000-0002-5653-199X)
- Marie Bordas (ORCID: https://orcid.org/0009-0007-6569-4305)
- Maria Grazia Marafioti (ORCID: https://orcid.org/0000-0002-9469-2110)
- Alessandro Giammona (ORCID: https://orcid.org/0000-0002-5978-2241)
- Matilde Todaro (ORCID: https://orcid.org/0000-0001-8686-8043)
- Yoshinori Fukasawa (ORCID: https://orcid.org/0000-0002-0882-4392)
- Giorgio Stassi (ORCID: https://orcid.org/0000-0002-1016-9059)
- Clelia Nisticò (ORCID: https://orcid.org/0000-0002-0787-9527)
- Jéssica Da Silva (ORCID: https://orcid.org/0000-0001-9305-4865)
- Luca Tirinato (ORCID: https://orcid.org/0000-0001-9826-2129)
- Fatema Alquraish (ORCID: https://orcid.org/0000-0001-6700-1524)
- Kendra K. Maaß (ORCID: https://orcid.org/0000-0001-9357-5038)
- Géraldine Genard (ORCID: https://orcid.org/0000-0002-9495-0335)
- Jeroen Krijgsveld (ORCID: https://orcid.org/0000-0001-7549-9326)
- Karsten Richter (ORCID: https://orcid.org/0000-0002-1049-8151)
- Maria Parra Reyes
- Torsten Müller
- Jeannette Janssen
Institutions
- German Cancer Research Center (DE)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- Magna Graecia University (IT)
- Institute of Molecular Bioimaging and Physiology (IT)
- Hopp Children's Cancer Center Heidelberg (DE)
- National Research Council (IT)
- King Abdullah University of Science and Technology (SA)
- University of Palermo (IT)
Publication Details
- Journal
- Journal of Extracellular Biology
- Published
- 2024-09-01
- DOI
- https://doi.org/10.1002/jex2.162
- Citations
- 5
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 1.17
Funders
- Deutscher Akademischer Austauschdienst
- King Abdullah University of Science and Technology
- Deutsche Krebshilfe
- HORIZON EUROPE Marie Sklodowska-Curie Actions