Magnetic resonance molecular imaging of metastatic breast cancer by targeting extradomain‐B fibronectin in the tumor microenvironment

Abstract

These findings potentiate the use of ZD2-Gd(HP-DO3A) for MR molecular imaging of malignant breast cancers to improve the healthcare of breast cancer patients. Magn Reson Med 79:3135-3143, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Overexpression of Extradomain-B Fibronectin is Associated with Invasion of Breast Cancer Cells

“…The specificity and superior binding of the ZD2 probe for EDB-FN has direct translational implications. We have successfully demonstrated differential diagnosis of non-invasive and invasive breast and prostate cancer xenografts in mouse models using ZD2-targeted MRI contrast agents [18,[23][24][25]. The results of this study open up new avenues for determining the potential of EDB-FN as a marker for molecular imaging-based detection, risk-stratification, active surveillance, and monitoring of breast cancers and tracking their evolution as the disease progresses with and without chemotherapy.…”

“…The overexpression of oncofetal fibronectin is correlated with histological grade in mammary tumors [ 12 ] and with poor survival in oral carcinoma patients [ 13 ]. Multiple lines of evidence show that EDB-FN is associated with epithelial-to-mesenchymal transition (EMT), cancer cell stemness, proliferation, angiogenesis, and metastasis, all of which reflect tumor aggressiveness [ 14 , 15 , 16 , 17 , 18 ]. Clinical studies demonstrate the presence of EDB-FN in patients with lung, brain, colorectal, ovarian, and thyroid cancers [ 19 , 20 , 21 ], suggesting its potential role as a marker for multiple neoplasms.…”

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

“…The specificity and superior binding of the ZD2 probe for EDB-FN has direct translational implications. We have successfully demonstrated differential diagnosis of non-invasive and invasive breast and prostate cancer xenografts in mouse models using ZD2-targeted MRI contrast agents (Han et al, 2017a, Han et al, 2018, Han et al, 2017b, Ayat et al, 2018). The results of this study open up new avenues for determining the potential of EDB-FN as a molecular biomarker for molecular imaging-based detection, risk-stratification, active surveillance, and monitoring of breast cancers and tracking their evolution as the disease progresses with and without chemotherapy.…”

“…Its alternative splice variant called extradomain-B fibronectin (EDB-FN), however, is known to be expressed during malignant transformation, and is generally absent from healthy adult tissues (White et al, 2008, Han and Lu, 2017). Multiple lines of evidence show that EDB-FN is associated with epithelial-to-mesenchymal transition (EMT), cancer cell stemness, proliferation, angiogenesis, and metastasis, all of which reflect tumor aggressiveness (Petrini et al, 2017, Sun et al, 2015, Tavian et al, 1994, Coltrini et al, 2009, Ventura et al, 2018, Han et al, 2018). Clinical studies demonstrate the presence of EDB-FN in patients with lung, brain, colorectal, ovarian, and thyroid cancers (Santimaria et al, 2003, Menzin et al, 1998, Giannini et al, 2003).…”

“…An added layer of complication is that even among the same cancer type, EDB-FN expression profiles are distinct and specific to the molecular and functional characteristics of the cells or tissues. For example, using an EDB-FN-specific peptide probe, ZD2-Cy5.5, we previously showed that invasive cancer cell lines, e.g., PC3 (prostate) and MDA-MB-231 (hormone receptor-negative breast cancer), are EDB-FN-rich, while the less invasive cancer cell lines, e.g., LNCaP (prostate) and MCF7 (hormone receptor-positive breast) exhibit significantly lower EDB-FN levels (Han et al, 2015, Han et al, 2017a, Han et al, 2018, Han et al, 2017b). 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).…”