Theranostics 2017; 7(14):3595-3607. doi:10.7150/thno.18974
Inhibition of Bone Marrow-Derived Mesenchymal Stem Cells Homing Towards Triple-Negative Breast Cancer Microenvironment Using an Anti-PDGFRβ Aptamer
1. Istituto per l'Endocrinologia e l'Oncologia Sperimentale "G. Salvatore", CNR, Naples, Italy;
2. Istituto di Biostrutture e Bioimmagini-CNR, Naples, Italy;
3. Ceinge, Advanced Biotechnology, Scarl, Naples, Italy;
4. Dipartimento di Scienze Biomediche Avanzate, Università degli Studi di Napoli "Federico II", Naples, Italy;
5. IRCCS SDN, Naples, Italy;
6. Istituto Ortopedico Rizzoli, Bologna, Italy.
* L. Cerchia and A. Zannetti contributed equally to this work.
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are shown to participate in tumor progression by establishing a favorable tumor microenvironment (TME) that promote metastasis through a cytokine networks. However, the mechanism of homing and recruitment of BM-MSCs into tumors and their potential role in malignant tissue progression is poorly understood and controversial. Here we show that BM-MSCs increase aggressiveness of triple-negative breast cancer (TNBC) cell lines evaluated as capability to migrate, invade and acquire stemness markers. Importantly, we demonstrate that the treatment of BM-MSCs with a nuclease-resistant RNA aptamer against platelet-derived growth factor receptor β (PDGFRβ) causes the inhibition of receptor-dependent signaling pathways thus drastically hampering BM-MSC recruitment towards TNBC cell lines and BM-MSCs trans-differentiation into carcinoma-associated fibroblast (CAF)-like cells. Moreover, in vivo molecular imaging analysis demonstrated the aptamer ability to prevent BM-MSCs homing to TNBC xenografts. Collectively, our results indicate the anti-PDGFRβ aptamer as a novel therapeutic tool to interfere with BM-MSCs attraction to TNBC providing the rationale to further explore the aptamer in more complex pre-clinical settings.
Keywords: Bone marrow-derived mesenchymal stem cells, aptamer, platelet-derived growth factor receptor β, triple-negative breast cancer.
Camorani S, Hill BS, Fontanella R, Greco A, Gramanzini M, Auletta L, Gargiulo S, Albanese S, Lucarelli E, Cerchia L, Zannetti A. Inhibition of Bone Marrow-Derived Mesenchymal Stem Cells Homing Towards Triple-Negative Breast Cancer Microenvironment Using an Anti-PDGFRβ Aptamer. Theranostics 2017; 7(14):3595-3607. doi:10.7150/thno.18974. Available from http://www.thno.org/v07p3595.htm