title: The evidence for and against different modes of tumour cell extravasation in the lung: diapedesis, capillary destruction, necroptosis, and endothelialization.
abstract: The development of lung metastasis is a significant negative prognostic factor for cancer patients. The extravasation phase of lung metastasis involves interactions of tumour cells with the pulmonary endothelium. These interactions may have broad biological and medical significance, with potential clinical implications ranging from the discovery of lung metastasis biomarkers to the identification of targets for intervention in preventing lung metastases. Because of the potential significance, the mechanisms of tumour cell extravasation require cautious, systematic studies. Here, we discuss the literature pertaining to the proposed mechanisms of extravasation and critically compare a recently proposed mechanism (tumour cell-induced endothelial necroptosis) with the already described extravasation mechanisms in the lung. We also provide novel data that may help to explain the underlying physiological basis for endothelialization as a mechanism of tumour cell extravasation in the lung. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
authors.affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.|Tumour Progression Research Group, Hungarian Academy of Sciences-Semmelweis University, Budapest, Hungary.
authors.forename: Sándor
authors.initials: S
authors.lastname: Paku
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Austria.|Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Austria.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Laszlo
authors.affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Dezso
authors.affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Nagy
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Austria.
authors.forename: Mir Alireza
authors.initials: MA
authors.lastname: Hoda
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Austria.|Department of Thoracic Surgery, Semmelweis University-National Institute of Oncology, Budapest, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Renyi-Vamos
authors.affiliation: Tumour Progression Research Group, Hungarian Academy of Sciences-Semmelweis University, Budapest, Hungary.|2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
authors.forename: Jozsef
authors.initials: J
authors.lastname: Timar
authors.affiliation: Tumour Biology Team, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Reynolds
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Austria.|Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Austria.|Department of Thoracic Surgery, Semmelweis University-National Institute of Oncology, Budapest, Hungary.|National Koranyi Institute of Pulmonology, Budapest, Hungary.
authors.forename: Balazs
authors.initials: B
authors.lastname: Dome
mesh_terms: D000818:Animals; D017209:Apoptosis; D001485:Basement Membrane / Q000473:pathology; D002196:Capillaries / Q000473:pathology; D002465:Cell Movement; D042783:Endothelial Cells / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D006801:Humans; D007962:Leukocytes / Q000473:pathology; D008168:Lung / Q000098:blood supply / Q000473:pathology; D008175:Lung Neoplasms / Q000209:etiology / Q000473:pathology / Q000556:secondary*; D009336:Necrosis; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D057705:Transendothelial and Transepithelial Migration
keywords: endothelialization; extravasation; lung; metastasis; necroptosis; tumour cell