Related Experiment Video
Updated: May 22, 2025

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
Published on: December 22, 2020
Extracellular Vesicles Secreted by Cancer-Associated Fibroblasts Drive Non-Invasive Cancer Cell Progression to
Adilson Fonseca Teixeira1,2, Yanhong Wang1, Josephine Iaria1,2
1Department of Surgery (The Royal Melbourne Hospital), The University of Melbourne, Parkville, Victoria, Australia.
Abstract:
Metastasis is the leading cause of cancer-related deaths. Cancer-associated fibroblasts (CAFs) are abundant components within the tumour microenvironment, playing critical roles in metastasis. Although increasing evidence supports a role for small extracellular vesicles (sEVs) in this process, their precise contribution and molecular mechanisms remain unclear, compromising the development of antimetastatic therapies. Here, we establish that CAF-sEVs drive metastasis by mediating CAF-cancer cell interaction and hyperactivating TGF-β signalling in tumour cells. Metastasis is abolished by genetically targeting CAF-sEV secretion and consequent reduction of TGF-β signalling in cancer cells. Pharmacological treatment with dimethyl amiloride (DMA) decreases CAFs' sEV secretion, reduces TGF-β signalling levels in tumour cells and abrogates metastasis and tumour self-seeding. This work defines a new mechanism required by CAFs to drive cancer progression, supporting the therapeutic targeting of EV trafficking to disable the driving forces of metastasis.
More Related Videos
Related Concept Videos
Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
The Tumor Microenvironment
Cancer Cell Migration through Invadopodia
Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...

