title: Cancer associated fibroblasts transfer lipids and proteins to cancer cells through cargo vesicles supporting tumor growth.
abstract: Fibroblasts are the most abundant cells in connective tissue and, with fibrillar extracellular matrix, form the structural scaffolding of organs. In solid tumors, interaction with cancer cells induces fibroblasts transdifferentiation into an activated form, which become a fundamental part of the tumor stroma. Within tumor microenvironment stromal and cancer cells engage a crosstalk that is mediated by soluble factors, cellcell contacts and extracellular vesicles trafficlking. Here we report that fibroblasts have the ability to transfer a remarkable amount of proteins and lipids to neighboring cells, in an ectosome-dependent fashion, identifying a novel and native property of these cells. Cancer-associated fibroblasts show an enhanced production and delivering of ectc:Jsomes to cancer cells compared to normal fibroblasts. As a consequence of this phenomenon, tumor cells increase their proliferation rate, indicating that ectosome-mediated trafficking could be a relevant mechanism mediating the trophic function of activated connective tissue on tumor cells.
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi di Firenze, 50134 Firenze, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Santi
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi di Firenze, 50134 Firenze, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Caselli
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi di Firenze, 50134 Firenze, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ranaldi
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi di Firenze, 50134 Firenze, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Paoli
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi di Firenze, 50134 Firenze, Italy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Mugnaioni
authors.affiliation: Mass Spectrometry Center, Università degli Studi di Firenze,, 50139 Firenze, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Michelucci
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi di Firenze, 50134 Firenze, Italy. Electronic address: paolo.cirri@unifi.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Cirri
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*; D021381:Protein Transport; D059016:Tumor Microenvironment
keywords: Cancer associated fibroblasts; Ectosomes; Extracellular vesicles; Microvesicles; Tumor microenvironment