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Survival-associated heterogeneity of marker-defined perivascular cells in colorectal cancer
Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.;Belarusian State Med Univ, Dept Pathol, Minsk, Byelarus..
Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
Oslo Univ Hosp, Dept Oncol, Oslo, Norway.;Oslo Univ Hosp, KG Jebsen Colorectal Canc Res Ctr, Oslo, Norway..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
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2016 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 27, 41948-41958 p.Article in journal (Refereed) Published
Abstract [en]

Perivascular cells (PC) were recently implied as regulators of metastasis and immune cell activity. Perivascular heterogeneity in clinical samples, and associations with other tumor features and outcome, remain largely unknown. Here we report a novel method for digital quantitative analyses of vessel characteristics and PC, which was applied to two collections of human metastatic colorectal cancer (mCRC). Initial analyses identified marker-defined subsets of PC, including cells expressing PDGFR-beta or alpha-SMA or both markers. PC subsets were largely independently expressed in a manner unrelated to vessel density and size. Association studies implied specific oncogenic mutations in malignant cells as determinants of PC status. Semi-quantitative and digital-image-analyses-based scoring of the NORDIC-VII cohort identified significant associations between low expression of perivascular PDGFR-alpha and -beta and shorter overall survival. Analyses of the SPCRC cohort confirmed these findings. Perivascular PDGFR-alpha and -beta remained independent factors for survival in multivariate analyses. Overall, our study identified host vasculature and oncogenic status as determinants of tumor perivascular features. Perivascular PDGFR-alpha and -beta were identified as novel independent markers predicting survival in mCRC. The novel methodology should be suitable for similar analyses in other tumor collections.

Place, publisher, year, edition, pages
2016. Vol. 7, no 27, 41948-41958 p.
Keyword [en]
PDGFR, perivascular cells, colorectal cancer, tumor stroma, cancer associated fibroblasts
National Category
Cancer and Oncology Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-308264DOI: 10.18632/oncotarget.9632ISI: 000380942600077PubMedID: 27248825OAI: oai:DiVA.org:uu-308264DiVA: diva2:1049320
Funder
Swedish Research Council
Available from: 2016-11-24 Created: 2016-11-24 Last updated: 2016-11-24Bibliographically approved

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Dragomir, AncaPontén, FredrikGlimelius, Bengt
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