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Pharmacological inhibition of syntenin PDZ2 domain impairs breast cancer cell activities and exosome loading with syndecan and EpCAM cargo.

Leblanc R, Kashyap R, Barral K, Egea-Jimenez AL, Kovalskyy D, Feracci M, Garcia M, Derviaux C, Betzi S, Ghossoub R, Platonov M, Roche P, Morelli X, Hoffer L, Zimmermann P
J Extracell Vesicles 10 e12039 (2020)
Cited: 15 times
EuropePMC logo PMID: 33343836

Abstract

Exosomes support cell-to-cell communication in physiology and disease, including cancer. We currently lack tools, such as small chemicals, capable of modifying exosome composition and activity in a specific manner. Building on our previous understanding of how syntenin, and its PDZ partner syndecan (SDC), impact on exosome composition we optimized a small chemical compound targeting the PDZ2 domain of syntenin. In vitro , in tests on MCF-7 breast carcinoma cells, this compound is non-toxic and impairs cell proliferation, migration and primary sphere formation. It does not affect the size or the number of secreted particles, yet it decreases the amounts of exosomal syntenin, ALIX and SDC4 while leaving other exosomal markers unaffected. Interestingly, it also blocks the sorting of EpCAM, a bona fide target used for carcinoma exosome immunocapture. Our study highlights the first characterization of a small pharmacological inhibitor of the syntenin-exosomal pathway, of potential interest for exosome research and oncology.

Articles - 6rlc mentioned but not cited (1)

  1. Pharmacological inhibition of syntenin PDZ2 domain impairs breast cancer cell activities and exosome loading with syndecan and EpCAM cargo. Leblanc R, Kashyap R, Barral K, Egea-Jimenez AL, Kovalskyy D, Feracci M, Garcia M, Derviaux C, Betzi S, Ghossoub R, Platonov M, Roche P, Morelli X, Hoffer L, Zimmermann P. J Extracell Vesicles 10 e12039 (2020)


Reviews citing this publication (10)

  1. Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer. Han QF, Li WJ, Hu KS, Gao J, Zhai WL, Yang JH, Zhang SJ. Mol Cancer 21 207 (2022)
  2. Current Knowledge on Exosome Biogenesis, Cargo-Sorting Mechanism and Therapeutic Implications. Xie S, Zhang Q, Jiang L. Membranes (Basel) 12 498 (2022)
  3. Exosomal transmission of viruses, a two-edged biological sword. Mardi N, Haiaty S, Rahbarghazi R, Mobarak H, Milani M, Zarebkohan A, Nouri M. Cell Commun Signal 21 19 (2023)
  4. From Exosome Biogenesis to Absorption: Key Takeaways for Cancer Research. Lau NCH, Yam JWP. Cancers (Basel) 15 1992 (2023)
  5. Glycocalyx Acts as a Central Player in the Development of Tumor Microenvironment by Extracellular Vesicles for Angiogenesis and Metastasis. Zeng Y, Qiu Y, Jiang W, Fu BM. Cancers (Basel) 14 5415 (2022)
  6. The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy. Alam MR, Rahman MM, Li Z. Genes Dis 11 321-334 (2024)
  7. Revisiting the Syndecans: Master Signaling Regulators with Prognostic and Targetable Therapeutic Values in Breast Carcinoma. Motta JM, Hassan H, Ibrahim SA. Cancers (Basel) 15 1794 (2023)
  8. Exosome-bearing hydrogels and cardiac tissue regeneration. Amini H, Namjoo AR, Narmi MT, Mardi N, Narimani S, Naturi O, Khosrowshahi ND, Rahbarghazi R, Saghebasl S, Hashemzadeh S, Nouri M. Biomater Res 27 99 (2023)
  9. Informed by Cancer Stem Cells of Solid Tumors: Advances in Treatments Targeting Tumor-Promoting Factors and Pathways. MacLean MR, Walker OL, Arun RP, Fernando W, Marcato P. Int J Mol Sci 25 4102 (2024)
  10. Tumorigenic and tumoricidal properties of exosomes in cancers; a forward look. Abbasi-Malati Z, Azizi SG, Milani SZ, Serej ZA, Mardi N, Amiri Z, Sanaat Z, Rahbarghazi R. Cell Commun Signal 22 130 (2024)

Articles citing this publication (4)

  1. Nuclear exosome HMGB3 secreted by nasopharyngeal carcinoma cells promotes tumour metastasis by inducing angiogenesis. Zhang K, Liu D, Zhao J, Shi S, He X, Da P, You Y, You B. Cell Death Dis 12 554 (2021)
  2. Homosalate boosts the release of tumour-derived extracellular vesicles with protection against anchorage-loss property. Grisard E, Nevo N, Lescure A, Doll S, Corbé M, Jouve M, Lavieu G, Lavieu G, Joliot A, Nery ED, Martin-Jaular L, Théry C. J Extracell Vesicles 11 e12242 (2022)
  3. Downregulation of stromal syntenin sustains AML development. Leblanc R, Ghossoub R, Goubard A, Castellano R, Fares J, Camoin L, Audebert S, Balzano M, Bou-Tayeh B, Fauriat C, Vey N, Garciaz S, Borg JP, Collette Y, Aurrand-Lions M, David G, Zimmermann P. EMBO Mol Med 15 e17570 (2023)
  4. Inhibitors against Two PDZ Domains of MDA-9 Suppressed Migration of Breast Cancer Cells. Tang H, Wang L, Li S, Wei X, Lv M, Zhong F, Liu Y, Liu J, Fu B, Zhu Q, Wang D, Liu J, Ruan K, Gao J, Xu W. Int J Mol Sci 24 3431 (2023)


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