Oral Presentation Australasia Extracellular Vesicles Conference 2017

Colorectal cancer exosomes promote fibroblast-led invasion of cancer cells (#20)

Alin Rai 1 , David Greening 1 , Rong Xu 1 , Maoshan Chen 1 , Richard Simpson 1
  1. Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia

Cancer associated fibroblasts (CAFs) are important mediators of cancer cell invasion and metastasis. They are found at the leading fronts of solid tumours where they lead invasion of cancer cells into surrounding tissues. Here we show that exosomes (30-150 nm extracellular vesicles), as distinct to soluble factors and shed microvesicles (100-1500 nm extracellular vesicles), from metastatic colorectal cancer (CRC) promote invasion of primary fibroblasts. Such exosomes were identified in tumour interstitial fluid and in vitro, trigger elevated expression of α-smooth muscle actin in fibroblasts, consistent with their activation towards a CAF-phenotype. Organotypic co-culture reveal that such fibroblasts lead invasion of primary cancer cells into the surrounding extracellular matrix, identifying exosomes as a novel mediator of fibroblast-led invasion. This novel mechanism of exosome-mediated stromal invasion could have important implications in invasive outgrowth and cancer metastasis.