EV-mediated communication in the tumor microenvironment Tumors are complex structures in which distinct cell types engage in intricate communication networks. The interactions between tumor and non-malignant stromal cells at the primary tumor as well as at distant metastatic sites have a crucial role in cancer progression. We discovered that bone cancer cells release high amounts of extracellular vesicles (EVs) that “educate” mesenchymal stem cells (MSC) to favor cancer growth and metastasis formation. This effect was due to a dramatic change in the inflammatory cytokine expression profile of the mesenchymal cells and could be revoked using specific anti-inflammatory drugs.
Using in vivo cancer models and next generation techniques, we are facing the new exciting challenge to: 1) Comprehensively study the immunomodulatory properties of tumor-educated stromal cells 2) Evaluate whether specific combinations of immunomodulatory drugs can block the pro-metastatic actions of cancer EVs 3) Identify circulating biomarkers for treatment response prediction in cancer patient plasma, with a particular focus on circulating EV-associated growth factors and non-coding RNAs.
Lagerweij T, Pérez-Lanzón M, Baglio SR. A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells. J Vis Exp. 2018 May 6.
Bebelman MP, Smit MJ, Pegtel DM, Baglio SR. Biogenesis and function of extracellular vesicles in cancer. Pharmacol Ther. 2018 Feb 21.
Baglio SR, Lagerweij T, Pérez Lanzón M, Xuan Ho D, Léveillé N, Melo SA, Cleton-Jansen AM, Jordanova ES, Roncuzzi L, Greco M, van Eijndhoven MA, Grisendi G, Dominici M, Bonafede R, Lougheed S, de Gruijl TD, Zini N, Cervo S, Steffan A, Canzonieri V, Martson A, Maasalu K, Koks S, Wurdinger T, Baldini N, Pegtel DM. Blocking tumor-educated MSC paracrine activity halts osteosarcoma progression. Clinical Cancer Research. 2017 Jan 4.
Baglio SR, Rooijers K, Koppers-Lalic D, Verweij FJ, Pérez Lanzón M, Zini N, Naaijkens B, Perut F, Niessen HW, Baldini N, Pegtel DM. Human bone marrow- and adipose-mesenchymal stem cells secrete exosomes enriched in distinctive miRNA and tRNA species. Stem Cell Res Ther. 2015 Jul 1;6:127.
Figure: Multiplex immunostaining of human osteosarcoma tumors showing high infiltration of immune cells with suppressive phenotypes.