1. Inhibition of Bone Marrow-Derived Mesenchymal Stem Cells Homing Towards Triple-Negative Breast Cancer Microenvironment Using an Anti-PDGFRβ Aptamer
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Matteo Gramanzini, Laura Cerchia, Luigi Auletta, Raffaela Fontanella, Billy Samuel Hill, Enrico Lucarelli, Simona Camorani, Adelaide Greco, Sandra Albanese, Antonella Zannetti, Sara Gargiulo, Camorani, S, Hill, B, Fontanella, R, Greco, A, Gramanzini, M, Auletta, L, Gargiulo, S, Albanese, S, Lucarelli, E, Cerchia, L, and Zannetti, A
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0301 basic medicine ,one marrow-derived mesenchymal stem cell ,Mice, Nude ,Medicine (miscellaneous) ,Triple Negative Breast Neoplasms ,Biology ,Bone marrow-derived mesenchymal stem cells ,Metastasis ,Receptor, Platelet-Derived Growth Factor beta ,Mice ,platelet-derived growth factor receptor β ,03 medical and health sciences ,0302 clinical medicine ,Triple-negative breast cancer ,Growth factor receptor ,Cell Movement ,Tumor Microenvironment ,medicine ,Animals ,Humans ,triple-negative breast cancer ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Cells, Cultured ,Mice, Inbred BALB C ,Tumor microenvironment ,Platelet-derived growth factor receptor ? ,Mesenchymal stem cell ,aptamer ,Mesenchymal Stem Cells ,Aptamers, Nucleotide ,Fibroblasts ,medicine.disease ,RNAi Therapeutics ,030104 developmental biology ,medicine.anatomical_structure ,Tumor progression ,030220 oncology & carcinogenesis ,Cell Transdifferentiation ,MCF-7 Cells ,Cancer research ,Female ,Bone marrow ,Research Paper ,Homing (hematopoietic) - Abstract
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 ? (PDGFR?) 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-PDGFR? 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.
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