Cancer associated fibroblasts transfer lipids and proteins to cancer cells through cargo vesicles supporting tumor growth.

Alice Santi, Anna Caselli, Francesco Ranaldi, Paolo Paoli, Camilla Mugnaioni, Elena Michelucci, Paolo Cirri

Index: Biochim. Biophys. Acta 1853 , 3211-23, (2015)

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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.Copyright © 2015 Elsevier B.V. All rights reserved.