Facial reconstruction

Search LJMU Research Online

Browse Repository | Browse E-Theses

Mesenchymal-epithelial signalling in tumour microenvironment: role of high-mobility group Box 1.

Sharma, S and Evans, AR and Hemers, E (2016) Mesenchymal-epithelial signalling in tumour microenvironment: role of high-mobility group Box 1. Cell and Tissue Research. ISSN 1432-0878

[img] Text
art%3A10.1007%2Fs00441-016-2389-7.pdf - Published Version

Download (830kB)

Abstract

Glucose deprivation, hypoxia and acidosis are characteristic features of the central core of most solid tumours. Myofibroblasts are stromal cells present in many such solid tumours, including those of the colon, and are known to be involved in all stages of tumour progression. HMGB1 is a nuclear protein with an important role in nucleosome stabilisation and gene transcription; it is also released from immune cells and is involved in the inflammatory process. We report that the microenvironmental condition of glucose deprivation is responsible for the active release of HMGB1 from various types of cancer cell lines (HT-29, MCF-7 and A549) under normoxic conditions. Recombinant HMGB1 (10 ng/ml) triggered proliferation in myofibroblast cells via activation of PI3K and MEK1/2. Conditioned medium collected from glucose-deprived HT-29 colon cancer cells stimulated the migration and invasion of colonic myofibroblasts, and these processes were significantly inhibited by immunoneutralising antibodies to HMGB1, RAGE and TLR4, together with specific inhibitors of PI3K and MEK1/2. Our data suggest that HMGB1 released from cancer cells under glucose deprivation is involved in stimulating colonic myofibroblast migration and invasion and that this occurs through the activation of RAGE and TLR4, resulting in the activation of the MAPK and PI3K signalling pathways. Thus, HMGB1 might be released by cancer cells in areas of low glucose in solid tumours with the resulting activation of myofibroblasts and is a potential therapeutic target to inhibit solid tumour growth.

Item Type: Article
Uncontrolled Keywords: 1116 Medical Physiology
Subjects: Q Science > QH Natural history > QH301 Biology
R Medicine > RS Pharmacy and materia medica
Divisions: Natural Sciences and Psychology
Pharmacy & Biomolecular Sciences
Publisher: Springer
Related URLs:
Date Deposited: 21 Mar 2016 10:59
Last Modified: 06 Sep 2017 23:32
DOI or Identification number: 10.1007/s00441-016-2389-7
URI: http://researchonline.ljmu.ac.uk/id/eprint/3301

Actions (login required)

View Item View Item