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Title: Nephronectin is Correlated with Poor Prognosis in Breast Cancer and Promotes Metastasis via its Integrin-Binding Motifs.
Austin Authors: Steigedal, Tonje S;Toraskar, Jimita;Redvers, Richard P;Valla, Marit;Magnussen, Synnøve N;Bofin, Anna M;Opdahl, Signe;Lundgren, Steinar;Eckhardt, Bedrich L;Lamar, John M;Doherty, Judy;Hynes, Richard O;Anderson, Robin L ;Svineng, Gunbjørg
Affiliation: Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, United States
David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States
Central Norway Regional Health Authority, Stjørdal, Norwa
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU, Trondheim, Norway
Department of Medical Biology, Faculty of Health Sciences, UiT - The Arctic University of Norway, Tromsø, Norway.
Cancer Clinic, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway
Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas at MD Anderson Cancer Centre, Houston, TX, USA
Section of Translational Breast Cancer Research, The University of Texas at MD Anderson Cancer Centre, Houston, TX, USA
Department of Breast Medical Oncology, The University of Texas at MD Anderson Cancer Centre, Houston, TX 77030, USA
School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia
Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, USA
Issue Date: Apr-2018
Date: 2018-03-11
Publication information: Neoplasia (New York, N.Y.) 2018; 20(4): 387-400
Abstract: Most cancer patients with solid tumors who succumb to their illness die of metastatic disease. While early detection and improved treatment have led to reduced mortality, even for those with metastatic cancer, some patients still respond poorly to treatment. Understanding the mechanisms of metastasis is important to improve prognostication, to stratify patients for treatment, and to identify new targets for therapy. We have shown previously that expression of nephronectin (NPNT) is correlated with metastatic propensity in breast cancer cell lines. In the present study, we provide a comprehensive analysis of the expression pattern and distribution of NPNT in breast cancer tissue from 842 patients by immunohistochemical staining of tissue microarrays from a historic cohort. Several patterns of NPNT staining were observed. An association between granular cytoplasmic staining (in <10% of tumor cells) and poor prognosis was found. We suggest that granular cytoplasmic staining may represent NPNT-positive exosomes. We found that NPNT promotes adhesion and anchorage-independent growth via its integrin-binding and enhancer motifs and that enforced expression in breast tumor cells promotes their colonization of the lungs. We propose that NPNT may be a novel prognostic marker in a subgroup of breast cancer patients.
DOI: 10.1016/j.neo.2018.02.008
ORCID: 0000-0002-6841-7422
Journal: Neoplasia (New York, N.Y.)
PubMed URL: 29539586
Type: Journal Article
Appears in Collections:Journal articles

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