Exosomal microRNAs derived from colorectal cancer-associated fibroblasts: role in driving cancer progression
Open accessAbstract
, we demonstrated that fibroblast exosomes are transferred to colorectal cancer cells, with a resultant increase in cellular microRNA levels, impacting proliferation and chemoresistance. To probe this further, exosomal microRNAs were profiled from paired patient-derived normal and cancer-associated fibroblasts, from an ongoing prospective biomarker study. An exosomal cancer-associated fibroblast signature consisting of microRNAs 329, 181a, 199b, 382, 215 and 21 was identified. Of these, miR-21 had highest abundance and was enriched in exosomes. Orthotopic xenografts established with miR-21-overexpressing fibroblasts and CRC cells led to increased liver metastases compared to those established with control fibroblasts. Our data provide a novel stromal exosome signature in colorectal cancer, which has potential for biomarker validation. Furthermore, we confirmed the importance of stromal miR-21 in colorectal cancer progression using an orthotopic model, and propose that exosomes are a vehicle for miR-21 transfer between stromal fibroblasts and cancer cells.
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CAFs are a substantial source of growth factors, cytokines and exosomes that can promote tumour growth and modulate therapy responses.
“CAFs are also a substantial source of growth factors, cytokines and exosomes that can promote tumour growth and modulate therapy responses27,106–108.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [106]
The Results report that CAF exosomes transfer to colorectal cancer cells, and the Discussion links exosomal miR-21 to cancer progression and mentions CAF-derived soluble factors (pages not provided). The paper does not establish that CAFs are a substantial source of growth factors and cytokines. Its direct oxaliplatin-resistance experiment used exosomes from a normal fibroblast line, not CAFs. (LLM, conf=0.84)
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- Authors
- Bhome, R., Goh, R. W., Bullock, M. D., Pillar, N., Thirdborough, S. M., Mellone, M., Mirnezami, R., Galea, D., Veselkov, K., Gu, Q., Underwood, T. J., Primrose, J. N., De Wever, O., Shomron, N., Sayan, A. E., & Mirnezami, A. H.
- Affiliations
- Southampton General Hospital (GB)
- Tel Aviv University (IL)
- Imperial College London (GB)
- MRC University of Glasgow Centre for Virus Research (GB)
- Cancer Sciences, University of Southampton, Somers Building, Southampton General Hospital, Southampton, SO16 6YD, UK
- University Surgical Unit, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK
- Department of Experimental Cancer Research, Ghent University, Radiotherapiepark, Ghent, 9000, Belgium
- ORCID
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2017-12-24
- Volume
- 9
- Issue
- 12
- Pages
- 2666-2694
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC5764398
- OpenAlex
- W2781198385
- Cited by
- 155
- References
- 78
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 16 · 2023: 14 · 2022: 15 · 2021: 30 · 2020: 41 · 2019: 17 · 2018: 6
- FWCI
- 7.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by
- Locations
- Aging (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Funders
- UK Research and Innovation
- Cancer Research UK (A20526, 23924, 20526, S_3319)
- National Institute for Health and Care Research (CL-2015-26-003, NF-SI-0515-10059, ACF-2012-26-005, CL-2013-21-012, ACF-2007-26-004)
- Research Councils UK
- University of Southampton
- Medical Research Council (MR/R002061/1)
- Biotechnology and Biological Sciences Research Council (BB/L020858/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- exosomal microRNAs, colorectal cancer, cancer-associated fibroblasts, miR-21, tumor microenvironment, liver metastasis, chemoresistance, tumor cell proliferation, exosome transfer, biomarkers, orthotopic xenograft
- MeSH terms
- Cancer-Associated Fibroblasts, Aged, Animals, Female, Humans, Male, Colorectal Neoplasms, Disease Progression, MicroRNAs, Mice, Exosomes, Heterografts
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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