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LIFR promotes tumor angiogenesis by up-regulating IL-8 levels in colorectal cancer
- Source :
- Biochimica et biophysica acta. Molecular basis of disease. 1864(9 Pt)
- Publication Year :
- 2018
-
Abstract
- Leukemia inhibitory factor receptor (LIFR) has been documented as a cancer promoter and to be present at high levels in various types of tumor tissues. In our search for molecules prognostic of colorectal cancer (CRC), we found high levels of LIFR in CRC tissue samples. Further analyses revealed that LIFR was indeed prognostic of CRC patient survival, and was associated with tumor size, lymphatic metastasis and stages. LIFR was found to promote tumor growth, metastasis and angiogenesis both in vitro and in vivo. High levels of LIFR in CRC facilitated proliferation and migration of endothelial cells, resulting in an increase in angiogenic activity. Moreover, interleukin 8 (IL-8) was found to play a role in the LIFR induced angiogenesis. IL-8 levels were correlated with LIFR levels in CRC tissues, whereas depletion of IL-8 led to a reduced angiogenic activity of LIFR in CRC cells. In addition, LIFR increased phosphorylation level of Erk, which regulates il-8 transcription. We conclude that LIFR is possibly a valuable prognostic marker for CRC. Our results also implicate a mechanism by which LIFR regulates tumor angiogenesis through Erk/IL-8 pathway, and that LIFR could be a potential therapeutic target for CRC.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Male
Leukemia Inhibitory Factor Receptor alpha Subunit
Angiogenesis
Colorectal cancer
Down-Regulation
Mice, Nude
Leukemia inhibitory factor receptor
Metastasis
03 medical and health sciences
Mice
0302 clinical medicine
Downregulation and upregulation
Cell Line, Tumor
medicine
Biomarkers, Tumor
Human Umbilical Vein Endothelial Cells
Animals
Humans
Interleukin 8
RNA, Small Interfering
Molecular Biology
Aged
Cell Proliferation
Neovascularization, Pathologic
Cell growth
business.industry
Interleukin-8
Endothelial Cells
Middle Aged
medicine.disease
Prognosis
Xenograft Model Antitumor Assays
digestive system diseases
Up-Regulation
030104 developmental biology
030220 oncology & carcinogenesis
Cancer research
Molecular Medicine
Female
business
Colorectal Neoplasms
Follow-Up Studies
Subjects
Details
- ISSN :
- 09254439
- Volume :
- 1864
- Issue :
- 9 Pt
- Database :
- OpenAIRE
- Journal :
- Biochimica et biophysica acta. Molecular basis of disease
- Accession number :
- edsair.doi.dedup.....ee0f4c55f47e628911a0d8f96b1619dd