Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877
AI Summary:
Intercellular communication between different cell types in solid tumors contributes to tumor growth and metastatic dissemination. Cancer-associated fibroblasts (CAFs) play major roles in these processes.AI Topics:
Intercellular communication between different cell types in solid tumors contributes to tumor growth and metastatic dissemination. The secretome of cancer-associated fibroblasts (CAFs) plays major roles in these processes. Using human mammary CAFs, we showed that CAFs with a myofibroblast phenotype released extracellular vesicles that transferred proteins to endothelial cells (ECs) that affected their interaction with immune cells. Mass spectrometry–based proteomics identified proteins transferred from CAFs to ECs, which included plasma membrane receptors. Using THY1 as an example of a transferred plasma membrane–bound protein, we showed that CAF-derived proteins increased the adhesion of a monocyte cell line to ECs. CAFs produced high amounts of matrix-bound EVs, which were the primary vehicles of protein transfer. Hence, our work paves the way for future studies that investigate how CAF-derived matrix-bound EVs influence tumor pathology by regulating the function of neighboring cancer, stromal, and immune cells.
Title | Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function |
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Creators | Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara |
Identification Number | 10.1126/scisignal.ade0580 |
Date | March 2024 |
Divisions | College of Medical Veterinary and Life Sciences > School of Cancer Sciences College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Publisher | American Association for the Advancement of Science |
Additional Information | This work was funded by Cancer Research UK Scotland Institute grant A31287, Cancer Research UK Glasgow Centre grant A18076, Cancer Research UK Beatson Institute Advanced Technology Facilities A17196, Stand Up to Cancer campaign for Cancer Research UK grant A29800 to S.Z., Cancer Research UK grants A29799 to K.B. and A23983 to L.M.C., and Breast Cancer Now project grants 2019AugPR1307 to S.Z. and 2019DecPR1424 to F.F. and L.M.C. |
URI | https://pub.demo35.eprints-hosting.org/id/eprint/357 |
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Item Type | Article |
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Depositing User | Unnamed user with email ejo1f20@soton.ac.uk |
Date Deposited | 11 Jun 2025 16:37 |
Revision | 30 |
Last Modified | 12 Jun 2025 10:13 |
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