The Role of Inflammatory Lipid Mediators on Colon Cancer Initiating Cells (CICs)
Author
Summary, in English
and augmented the colonies formation and tumor progression in xenograft mice model. The ALDH+ cells were also resistant to 5-fluorouracil and radiation that is additionally augmented by both the lipid-mediators. Moreover
the impact of lipid inflammatory mediators on the stemness properties of CICs was evident by increased expression of genes that confer survival and self-renewal ability to CICs. In immunodeficient mice, LTD4 or PGE2
treatment amplified CIC-induced tumor growth. Furthermore, LTD4 and PGE2 increased cell proliferation activated β-catenin signaling and up-regulated COX-2. Additionally, LTD4 or PGE2 drive massive inflammatory responses identified as CD45+ enrichment, particularly of macrophages within tumors. The ability of ALDH+ cells to form tumors in immunodeficient mice could not be challenged by radiation therapy.
In a separate series of experiments, we investigated the contribution of CICs in the development of sensitivity against montelukast, a CysLT1R antagonist. In this context we report that sensitivity of tumors against
montelukast could depend on the variation in CICs content, activation of prosurvival factors such as BCL-2 and β-catenin signaling. Collectively, our data showed that LTD4 and PGE2 exacerbate CIC characteristics and promote
tumor growth by allowing modifications in the tumor environment. New therapeutic strategies could aim to resolve not only cancer associated inflammation, but also to target CICs in order to achieve better remission and cure advanced colon cancer stages.
Department/s
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Cell Pathology, Malmö
Publishing year
2015
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2015:18
Full text
- Available as PDF - 32 MB
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Document type
Dissertation
Publisher
Department of Laboratory Medicine, Lund University
Topic
- Clinical Medicine
Status
Published
Research group
- Cell Pathology, Malmö
Supervisor
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-7619-071-5
Defence date
16 January 2015
Defence time
09:00
Defence place
Auditoriet, plan 3, Jan Waldenströms gata 47, Skånes Universitetssjukhus, Malmö.
Opponent
- Johan Holmberg (Dr.)