Open AccessActivated fibroblasts enhance cancer cell migration by microvesicles‐mediated transfer of Galectin‐1
Author(s) -
Toti Alessandra,
Santi Alice,
Pardella Elisa,
Nesi Ilaria,
Tomasini Richard,
Mello Tommaso,
Paoli Paolo,
Caselli Anna,
Cirri Paolo
Publication year - 2021
Publication title -
journal of cell communication and signaling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 44
eISSN - 1873-961X
pISSN - 1873-9601
DOI - 10.1007/s12079-021-00624-4
Subject(s) - microvesicles , tumor microenvironment , microbiology and biotechnology , cancer associated fibroblasts , cancer cell , stromal cell , tumor progression , crosstalk , biology , chemistry , cancer research , cancer , microrna , tumor cells , biochemistry , genetics , physics , gene , optics
Cancer‐associated fibroblasts (CAFs) are one of the main components of the stromal compartment in the tumor microenvironment (TME) and the crosstalk between CAFs and cancer cells is essential for tumor progression and aggressiveness. Cancer cells mediate an activation process, converting normal fibroblasts into CAFs, that are characterized by modified expression of many proteins and increased production and release of microvesicles (MVs), extracellular vesicles generated by outwards budding from the cell membrane. Recent evidence underlined that the uptake of CAF‐derived MVs changes the overall protein content of tumor cells. In this paper, we demonstrate that tumor activated fibroblasts overexpress Galectin‐1 (Gal‐1) and consequently release MVs containing increased levels of this protein. The uptake of Gal‐1 enriched MVs by tumor cells leads to the upregulation of its intracellular concentration, that strongly affects cancer cell migration, while neither proliferation nor adhesion are altered. Accordingly, tumor cells co‐cultured with fibroblasts silenced for Gal‐1 have a reduced migratory ability. The present work reveals the key role of an exogenous protein, Gal‐1, derived from activated fibroblasts, in cancer progression, and contributes to clarify the importance of MVs‐mediated protein trafficking in regulating tumor‐stroma crosstalk.