NDLI: Interleukin-1 receptor antagonist inhibits metastatic potential by down-regulating CXCL12/CXCR4 signaling axis in colorectal cancer

Content Provider	Springer Nature : BioMed Central
Author	Ma, Jiachi Liang, Wanqing Qiang, Yaosheng Li, Lei Du, Jun Pan, Chengwu Chen, Bangling Zhang, Chensong Chen, Yuzhong Wang, Qingkang
Abstract	Background The aim of this study was to investigate the co-operative role of CXCR4/CXCL12 axis and IL-1Ra in metastatic processes mechanism by interactions between colorectal cancer cells and stromal cells in their microenvironment. Methods Expression of IL-1α, interleukin-1 receptor type I (IL-1 RI), CXCL12 and CXCR4 mRNA and proteins were determined by RT-PCR and Western blot. The effect of secreted level of CXCL12 by IL-1Ra on fibroblasts was measured by ELISA. CXCL12 regulate metastatic potential of colorectal cancer was evaluated by proliferation, invasion and angiogenesis assays, respectively, in which invasion and angiogenesis assays used an in vitro system consisting of co-cultured colorectal cells and stromal cells. Results IL-1α was expressed in high liver metastatic colorectal cancer cell lines (HT-29 and WiDr). The colorectal cancer cell-derived IL-1α and rIL-1α significantly promoted CXCL12 expression by fibroblasts, and this enhancing effect can be significantly inhibited by IL-1Ra (P < 0.01). CXCL12 not only enhanced the migration and proliferation of human umbilical vein endothelial cells, but also significantly enhanced angiogenesis (P < 0.01). Furthermore, the high liver-metastatic colorectal cancer cell line (HT-29), which secretes IL-1α, significantly enhanced angiogenesis compared to the low liver-metastatic cell line (CaCo-2), which does not produce IL-1α (P < 0.01). On the contrary, IL-1Ra can significantly inhibit migration, proliferation and angiogenesis (P < 0.01). Conclusion Autocrine IL-1α and paracrine CXCL12 co-enhances the metastatic potential of colorectal cancer cells; IL-1Ra can inhibit the metastatic potential of colorectal cancer cells via decrease IL-1α/CXCR4/CXCL12 signaling pathways. Graphical Abstract Video Abstract
Related Links	https://biosignaling.biomedcentral.com/counter/pdf/10.1186/s12964-021-00804-0.pdf
Ending Page	13
Page Count	13
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s12964-021-00804-0
Journal	Cell Communication and Signaling
Issue Number	1
Volume Number	19
Language	English
Publisher	BioMed Central
Publisher Date	2021-12-20
Access Restriction	Open
Subject Keyword	Cell Biology Protein-Ligand Interactions Receptors Cytokines and Growth Factors Interleukin-1 receptor antagonist CXCR4-CXCL12 axis Colorectal cancer Metastasis
Content Type	Text
Resource Type	Article
Subject	Biochemistry Cell Biology Molecular Biology
Journal Impact Factor	8.2/2023
5-Year Journal Impact Factor	8/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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