Current Biology
Volume 21, Issue 9, 10 May 2011, Pages 779-786
Journal home page for Current Biology

Report
Amphiregulin Exosomes Increase Cancer Cell Invasion

https://doi.org/10.1016/j.cub.2011.03.043Get rights and content
Under an Elsevier user license
open archive

Summary

Autocrine, paracrine, and juxtacrine are recognized modes of action for mammalian EGFR ligands including EGF, TGF-α (TGFα), amphiregulin (AREG), heparin-binding EGF-like growth factor (HB-EGF), betacellulin, epiregulin, and epigen. We identify a new mode of EGFR ligand signaling via exosomes. Human breast and colorectal cancer cells release exosomes containing full-length, signaling-competent EGFR ligands. Exosomes isolated from MDCK cells expressing individual full-length EGFR ligands displayed differential activities; AREG exosomes increased invasiveness of recipient breast cancer cells 4-fold over TGFα or HB-EGF exosomes and 5-fold over equivalent amounts of recombinant AREG. Exosomal AREG displayed significantly greater membrane stability than TGFα or HB-EGF. An average of 24 AREG molecules are packaged within an individual exosome, and AREG exosomes are rapidly internalized by recipient cells. Whether the composition and behavior of exosomes differ between nontransformed and transformed cells is unknown. Exosomes from DLD-1 colon cancer cells with a mutant KRAS allele exhibited both higher AREG levels and greater invasive potential than exosomes from isogenically matched, nontransformed cells in which mutant KRAS was eliminated by homologous recombination. We speculate that EGFR ligand signaling via exosomes might contribute to diverse cancer phenomena such as field effect and priming of the metastatic niche.

Highlights

► EGFR ligands are present in exosomes released by human cancer cells ► AREG exosomes increase cancer cell invasion more than HB-EGF or TGFα exosomes ► AREG exosomes are rapidly internalized by recipient cells ► KRAS status correlates with AREG levels in exosomes and their invasive potential

Cited by (0)

7

These authors contributed equally to this work