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Tumor Vessel Up-Regulation of INSR Revealed by Single-Cell Expression Analysis of the Tyrosine Kinome and Phosphatome in Human Cancers
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
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.
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.
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.
2015 (English)In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 185, no 6, 1600-1609 p.Article in journal (Refereed) Published
Abstract [en]

The tyrosine kinome and phosphatome harbor oncogenes and tumor suppressor genes and important regulators of angiogenesis and tumor stroma formation. To provide a better understanding of their potential roles in cancer, we analyzed the expression of 85 tyrosine kinases and 42 tyrosine phosphatases by in situ hybridization 48 human normal and 24 tumor tissue specimens. Nine-tenths of the assessed transcripts had tumor cell expression concordant with expression array databases. Further, pan-cancer expression of AATK, PTPRK, and PTPRU and expression of PTPRS in a subset of tumors were observed. To demonstrate tumor subcompartment resolution, we validated the predicted tumor stroma-specific markers HTRA1, HTRA3, MXRA5, MXRA8, and SERPING1 in situ. In addition to known vascular and stromal markers such as PDGERB, we observed stromal expression of PTK6 and TNS1 and vascular expression of INSR, PTPRF, PTPRG, PTPRU, and TNS1, of which INSR emerged as a tumor-specific vessel marker. This study demonstrates the feasibility of Large-scale analyses to chart the transcriptome in situ in human cancers and their ability to identify novel cancer biomarkers.

Place, publisher, year, edition, pages
2015. Vol. 185, no 6, 1600-1609 p.
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-257001DOI: 10.1016/j.ajpath.2015.02.019ISI: 000355350500011PubMedID: 25864925OAI: oai:DiVA.org:uu-257001DiVA: diva2:831779
Available from: 2015-06-30 Created: 2015-06-29 Last updated: 2017-12-04Bibliographically approved

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Ljungström, ViktorPontén, FredrikSjöblom, Tobias

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