MRI of Breast Tumor Initiating Cells Using the Extra Domain-B of Fibronectin Targeting Nanoparticles

Sun, Yj Sun Yujin; Kim, Hs Kim Hoe Suk; Park, Jinho Park; Li, Mulan Li; Tian, Lianji; Choi, YoonSeok Choi; Choi, Bi Choi Byung Ihn; Jon, Sangyong; Moon, WK

doi:10.7150/thno.8343

Cited by 27 publications

(33 citation statements)

References 35 publications

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“…APT EDB -TCL-SPIO nanoparticles showed significant accumulation in breast tumor initiating cells, NDY-1, with specific overexpression of EDB-FN. In contrast, APT EDB -TCL-SPIO, could not bind to non-breast tumor initiating cells, such MCF-7 cells, which had low EDB-FN expression 103 .…”

Section: Targeting Fibronectin For Cancer Imagingmentioning

confidence: 82%

“…It has been shown that CREKA-SPIO could induce additional plasma clotting in tumor, producing binding sites for more nanoparticles. This clotting-based amplification greatly enhanced tumor imaging 98, 99, 103 . Preparation of the APT EDB labeled SPION nanoparticles is depicted in Figure 6.…”

Section: Targeting Fibronectin For Cancer Imagingmentioning

confidence: 98%

“…Besides Gd-based contrast agents, FN-targeting peptides, including CREKA and APT EDB , have also been used to modify super paramagnetic iron oxide nanoparticles (SPIO) for T 2 *-weighted MR molecular imaging 98, 99, 103 . It has been shown that CREKA-SPIO could induce additional plasma clotting in tumor, producing binding sites for more nanoparticles.…”

Section: Targeting Fibronectin For Cancer Imagingmentioning

confidence: 99%

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Targeting fibronectin for cancer imaging and therapy

2017

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During cancer progression, the extracellular matrix (ECM) undergoes dramatic changes, which promote cancer cell migration and invasion. In the remodeled tumor ECM, fibronectin (FN) level is upregulated to assist tumor growth, progression, and invasion. FN serves as a central organizer of ECM molecules and mediates the crosstalk between the tumor microenvironment and cancer cells. Its upregulation is correlated with angiogenesis, cancer progression, metastasis, and drug resistance. A number of FN-targeting ligands have been developed for cancer imaging and therapy. Thus far, FN-targeting imaging agents have been tested for nuclear imaging, MRI, and fluorescence imaging, for tumor detection and localization. FN-targeting therapeutics, including nuclear medicine, chemotherapy drugs, cytokines, and photothermal moieties, were also developed in cancer therapy. Because of the prevalence of FN overexpression in cancer, FN targeting imaging agents and therapeutics have the promise of broad applications in the diagnosis, treatment, and image-guided interventions of many types of cancers. This review will summarize current understanding on the role of FN in cancer, discuss the design and development of FN-targeting agents, and highlight the applications of these FN-targeting agents in cancer imaging and therapy.

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Section: Targeting Fibronectin For Cancer Imagingmentioning

confidence: 82%

Section: Targeting Fibronectin For Cancer Imagingmentioning

confidence: 98%

Section: Targeting Fibronectin For Cancer Imagingmentioning

confidence: 99%

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Targeting fibronectin for cancer imaging and therapy

2017

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“…Previous studies have already demonstrated the potential of antibody-mediated EDB-FN targeting (using L19, BC-1) for angiogenesis, inflammation, and cancer stem cell therapy (Mariani et al, 1997, Tijink et al, 2009). EDB-FN-specific peptides, such as ZD2 and APT EDB , are advantageous for oncogenic ECM targeting, by virtue of their small size, low immunogenicity, and high tissue penetration ability (Han et al, 2015, Sun et al, 2014, Zahnd et al, 2010). The specificity and superior binding of the ZD2 probe for EDB-FN has direct translational implications.…”

Section: Discussionmentioning

confidence: 99%

“…This differential expression of EDB-FN was exploited for differentially diagnosing invasive prostate and breast cancer tumors from the non-invasive xenografts using EDB-FN-targeted MRI contrast agents (Ayat et al, 2018, Han et al, 2017a, Han et al, 2017b). Other independent groups have also used EDB-FN as a molecular target for targeted imaging and therapeutic delivery for various types of cancer (Sun et al, 2014, Ye et al, 2017, Han et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Extradomain-B Fibronectin is a molecular marker of invasive breast cancer cells

Vaidya

Wang

Qian

et al. 2019

Preprint

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invasiveness 28 Abbreviations 29 BCa -Breast cancer 30 EDB-FN -Extradomain-B fibronectin 31 FN1 -Fibronectin 32 MRI -Magnetic resonance imaging 33 PET -Positron-emission tomography 34 CT -Computed tomography 35 TME -Tumor microenvironment 36 ECM -Extracellular matrix 37 TGF-β -Transforming growth factor-β 38 EMT -Epithelial to mesenchymal transition 39 CEA -Carcinoembryonic antigen 40 41 42 43 44 45 46 47 48 49 50 51 Summary Statement 52 Dynamic changes in invasive properties of breast cancer cells directly influence extradomain-B 53 fibronectin levels, suggesting its potential role as a molecular marker for active surveillance and 54 therapeutic monitoring of breast cancer. 55 Abstract 56Breast tumor heterogeneity is a major impediment to oncotherapy. Tumor cells undergo rapid 57 clonal evolution, thereby acquiring significant growth and invasive advantages. The absence of 58 specific markers of these high-risk tumors precludes efficient therapeutic and diagnostic 59 management of breast cancer. Given the critical function of tumor microenvironment in the 60 oncogenic circuitry, we sought to determine the role of the extracellular matrix oncoprotein, 61 extradomain-B fibronectin (EDB-FN), as a molecular marker of aggressive cancers. High-risk 62 invasive cell lines generated from relatively less invasive MCF7 and MDA-MB-468 breast cancer 63 cells by long-term TGF-β treatment and chemoresistance demonstrated hybrid epithelial-64 mesenchymal phenotype, enhanced motility, and significantly elevated EDB-FN levels in 2D-and 65 3D-cultures. To determine if EDB-FN could serve as a therapy-predictive marker, the invasive cell 66 lines were treated with MK2206-HCl, a pan-AKT inhibitor. Phospho-AKT depletion reduced 67 EMT and invasion of the populations, with a concomitant decrease in EDB-FN expression, partly 68 through the phosphoAKT-SRp55 pathway, demonstrating that EDB-FN expression is strongly 69 associated with high-risk breast cancer. EDB-FN is a promising molecular marker for accurate 70 detection, differential diagnosis, and non-invasive therapeutic surveillance of aggressive breast 71 cancer. 72 73 74 75 76 77 78 79Breast cancer (BCa) is a devastating disease that accounts for 41,000 deaths each year in 80 the US (Siegel et al., 2018). Although the survival rate for patients with localized BCa is close to 81 99%, it declines precipitously in patients with distant metastases and drug resistance (Siegel et al., 82 2018, DeSantis et al., 2017). A major stumbling block in the clinical management of the disease 83 is tumor heterogeneity, which plays a role in the dynamic nature of BCa progression (Baird and 84 Caldas, 2013). Whole genome sequencing and profiling studies have demonstrated that breast 85 tumors of the same histological subtype exhibit distinct molecular portraits and discrete trajectories 86 in individual BCa patients at different stages (Tsang and Tse, 2019, Eliyatkin et al., 2015, Baird 87 and Caldas, 2013). Stochastic mutations, genome instability, and clonal evolution arising from 88 selective pre...

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