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

• Fibroblasts transfer lipids and proteins to neighboring cells.
• Upon activation fibroblasts increase proteins delivery to epithelial cells.
• CAFs transfer protein and lipids to cancer cells through ectosomes.
• Ectosomes-mediated protein flux enhance tumor cell proliferation.

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, cell–cell contacts and extracellular vesicles trafficking.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 ectosomes 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.

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