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.
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
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.