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A stromal cell population in the large intestine identified by tissue factor expression that is lost during colorectal cancer progression
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Human Prot Atlas Project, Lab Surgpath, Mumbai Site, Bombay, Maharashtra, India..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2016 (English)In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 116, no 6, 1050-1059 p.Article in journal (Refereed) Published
Abstract [en]

Colorectal cancer (CRC) is a major cause of morbidity and mortality, and the composition of the tumour stroma is a strong predictor of survival in this cancer type. Tissue factor (TF) functions as the trigger of haemostasis together with its ligand coagulation factor VII/ VIIa, and TF expression has been found in tumour cells of colorectal tumours. However, TF expression in the CRC tumour stroma or its relationship to patient outcome has not yet been studied. To address this question we developed and validated a specific anti-TF antibody using standardised methods within the Human Protein Atlas project. We used this antibody to investigate TF expression in normal colorectal tissue and CRC using immunofluorescence and immunohistochemistry in two patient cohorts. TF was strongly expressed in a cell population immediately adjacent to the colorectal epithelium. These TF-positive cells were ACTA2-negative but weakly vimentin-positive, defining a specific population of pericryptal sheath cells. In colorectal tumours, TF-positive sheath cells were progressively lost after the adenoma-to-carcinoma transition, demonstrating downregulation of this source of TF in CRC. Furthermore, loss of sheath cell TF was significantly associated with poor overall and disease-specific survival in rectal but not colon cancers. In conclusion, we demonstrate that TF is a marker of a specific cell population in the large intestine, which is lost during CRC progression. Our results highlight the role of the tumour stroma in this cancer type and suggest TF to be a potential prognostic biomarker in rectal cancers through the identification of pericryptal sheath cells.

Place, publisher, year, edition, pages
2016. Vol. 116, no 6, 1050-1059 p.
Keyword [en]
Tissue microarray, Tissue Factor/factor VII, immunohistochemistry, biomarker, colorectal cancer
National Category
Hematology Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:uu:diva-311183DOI: 10.1160/TH16-04-0267ISI: 000388968700007PubMedID: 27656710OAI: oai:DiVA.org:uu-311183DiVA: diva2:1059343
Funder
Swedish Research CouncilScience for Life Laboratory - a national resource center for high-throughput molecular bioscienceKnut and Alice Wallenberg Foundation
Available from: 2016-12-22 Created: 2016-12-22 Last updated: 2016-12-22Bibliographically approved

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Eriksson, OskarAsplund, AnnaEdqvist, Per-Henrik DPonten, FredrikSiegbahn, A
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Science for Life Laboratory, SciLifeLabCoagulation and inflammation scienceDepartment of Immunology, Genetics and PathologyExperimental and Clinical OncologyDepartment of Medical Biochemistry and Microbiology
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Thrombosis and Haemostasis
HematologyCardiac and Cardiovascular Systems

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