Abstract
Recent progress in breast cancer research has led to the identification of Vascular Cell Adhesion Molecule-1 (VCAM-1) as a key actor of metastatic colonization. VCAM-1 promotes lung-metastases and is associated with clinical early recurrence and poor outcome in triple negative breast cancer (TNBC). Our objective was to perform the in vivo imaging of VCAM-1 in mice models of TNBC. The Cancer Genomic Atlas (TCGA) database was analyzed to evaluate the prognostic role of VCAM-1 in TNBC. MDA-MB-231 (VCAM-1+) and control HCC70 (VCAM-1-) TNBC cells were subcutaneously xenografted in mice and VCAM-1 expression was assessed in vivo by single-photon emission computed tomography (SPECT) imaging using 99mTc-cAbVCAM1-5. Then, MDA-MB-231 cells were intravenously injected in mice and VCAM-1 expression in lung metastasis was assessed by SPECT imaging after 8 weeks. TCGA analysis showed that VCAM-1 is associated with a poor prognosis in TNBC patients. In subcutaneous tumor models, 99mTc-cAbVCAM1-5 uptake was 2-fold higher in MDA-MB-231 than in HCC70 (p < 0.01), and 4-fold higher than that of the irrelevant control (p < 0.01). Moreover, 99mTc-cAbVCAM1-5 uptake in MDA-MB-231 lung metastases was also higher than that of 99mTc-Ctl (p < 0.05). 99mTc-cAbVCAM1-5 is therefore a suitable tool to evaluate the role of VCAM-1 as a marker of tumor aggressiveness of TNBC.
Highlights
Breast cancer (BC) is the most common female malignancy, accounting for more than 30% of all malignant tumors in women [1]
Vascular Cell Adhesion Molecule-1 (VCAM-1) Is Overexpressed in triple negative breast cancer (TNBC) and Associated with Decreased overall survival (OS)
VCAM-1 expression was associated with decreased OS in TNBC but not in non-TNBC patients
Summary
Breast cancer (BC) is the most common female malignancy, accounting for more than 30% of all malignant tumors in women [1]. Breast cancer is a heterogeneous disease consisting of various subtypes with distinct molecular and pathological profiles [2,3]. Subtypes represent 10% to 20% of BC and are characterized by the lack of progesterone receptor, Cancers 2019, 11, 1039; doi:10.3390/cancers11071039 www.mdpi.com/journal/cancers. TNBC are mostly associated with poor clinical outcome and high rate of metastasis and relapse following treatment [5,6]. Bones, brain and liver are the most common sites of distant metastasis. Despite intense clinical research efforts, only limited advances have been obtained in the management of BC metastases
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