Intravital imaging reveals systemic ezrin inhibition impedes cancer cell migration and lymph node metastasis in breast cancer.
Background: Limited understanding of the cancer biology of metastatic sites is a major factor contributing to poor outcomes in cancer patients. The regional lymph nodes are the most common site of metastasis in most solid cancers and their involvement is a strong predictor of relapse in breast cance...
| Publicado en: | Breast Cancer Research Vol. 21; no. 1 |
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| Autores principales: | , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
BioMed Central
1/24/2019
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=134277569&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 134277569 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14655411 8UYJ jtl: Breast Cancer Research issn: 14655411 maglogo: N pubinfo: dt: 1/24/2019 vid: 21 iid: 1 pid: 24147 pub: BioMed Central artinfo: ui: 134277569 134277569 NLM30678714 134277569 10.1186/s13058-018-1079-7 NLM30678714 134277569 ppct: 1 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Intravital imaging reveals systemic ezrin inhibition impedes cancer cell migration and lymph node metastasis in breast cancer. aug: au: Ghaffari, Abdi Hoskin, Victoria Turashvili, Gulisa Varma, Sonal Mewburn, Jeff Mullins, Graeme Greer, Peter A. Kiefer, Friedemann Day, Andrew G. Madarnas, Yolanda SenGupta, Sandip Elliott, Bruce E. affil: Department of Pathology and Molecular Medicine, Queen's University, Kingston, Canada sug: subj: Cytoskeletal Proteins Metabolism Lung Neoplasms Pathology Breast Neoplasms Pathology Neoplasm Recurrence, Local Pathology Antiinfective Agents, Quinolone Pharmacodynamics Animal Studies Breast Pathology Lung Middle Age Cytoskeletal Proteins Antagonists and Inhibitors Phenols Pharmacodynamics Models, Biological Genes Tissue Array Analysis Antineoplastic Agents Therapeutic Use Lung Pathology Lymph Nodes Drug Effects Cell Movement Drug Effects Mice Neoplasm Metastasis Prevention and Control Lymph Nodes Pathology Neoplasm Metastasis Prospective Studies Antineoplastic Agents Pharmacodynamics Neoplasm Metastasis Pathology Human Lung Neoplasms Breast Neoplasms Cell Line, Tumor Transplantation Antiinfective Agents, Quinolone Therapeutic Use Phenols Therapeutic Use Female Lymph Nodes Validation Studies Comparative Studies Evaluation Research Multicenter Studies Middle Aged: 45-64 years Female ab: Background: Limited understanding of the cancer biology of metastatic sites is a major factor contributing to poor outcomes in cancer patients. The regional lymph nodes are the most common site of metastasis in most solid cancers and their involvement is a strong predictor of relapse in breast cancer (BC). We have previously shown that ezrin, a cytoskeletal-membrane linker protein, is associated with lymphovascular invasion and promotes metastatic progression in BC. However, the efficacy of pharmacological inhibition of ezrin in blocking cancer cell migration and metastasis remains unexplored in BC.Methods: We quantified ezrin expression in a BC tissue microarray (n = 347) to assess its correlation with risk of relapse. Next, we developed a quantitative intravital microscopy (qIVM) approach, using a syngeneic lymphatic reporter mouse tumor model, to investigate the effect of systemic ezrin inhibition on cancer cell migration and metastasis.Results: We show that ezrin is expressed at significantly higher levels in lymph node metastases compared to matched primary tumors, and that a high tumor ezrin level is associated with increased risk of relapse in BC patients with regional disease. Using qIVM, we observe a subset of cancer cells that retain their invasive and migratory phenotype at the tumor-draining lymph node. We further show that systemic inhibition of ezrin, using a small molecule compound (NSC668394), impedes the migration of cancer cells in vivo. Furthermore, systemic ezrin inhibition leads to reductions in metastatic burden at the distal axillary lymph node and lungs.Conclusions: Our findings demonstrate that the tumor ezrin level act as an independent biomarker in predicting relapse and provide a rationale for therapeutic targeting of ezrin to reduce the metastatic capacity of cancer cells in high-risk BC patients with elevated ezrin expression. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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