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01-03-2008 | Lab Investigation - human/animal tissue

HMGB1 as an autocrine stimulus in human T98G glioblastoma cells: role in cell growth and migration

Authors: Rosaria Bassi, Paola Giussani, Viviana Anelli, Thomas Colleoni, Marco Pedrazzi, Mauro Patrone, Paola Viani, Bianca Sparatore, Edon Melloni, Laura Riboni

Published in: Journal of Neuro-Oncology | Issue 1/2008

Abstract

HMGB1 (high mobility group box 1 protein) is a nuclear protein that can also act as an extracellular trigger of inflammation, proliferation and migration, mainly through RAGE (the receptor for advanced glycation end products); HMGB1–RAGE interactions have been found to be important in a number of cancers. We investigated whether HMGB1 is an autocrine factor in human glioma cells. Western blots showed HMGB1 and RAGE expression in human malignant glioma cell lines. HMGB1 induced a dose-dependent increase in cell proliferation, which was found to be RAGE-mediated and involved the MAPK/ERK pathway. Moreover, in a wounding model, it induced a significant increase in cell migration, and RAGE-dependent activation of Rac1 was crucial in giving the tumour cells a motile phenotype. The fact that blocking DNA replication with anti-mitotic agents did not reduce the distance migrated suggests the independence of the proliferative and migratory effects. We also found that glioma cells contain HMGB1 predominantly in the nucleus, and cannot secrete it constitutively or upon stimulation; however, necrotic glioma cells can release HMGB1 after it has translocated from the nucleus to cytosol. These findings provide the first evidence supporting the existence of HMGB1/RAGE signalling pathways in human glioblastoma cells, and suggest that HMGB1 may play an important role in the relationship between necrosis and malignancy in glioma tumours by acting as an autocrine factor that is capable of promoting the growth and migration of tumour cells.

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Title: HMGB1 as an autocrine stimulus in human T98G glioblastoma cells: role in cell growth and migration
Authors: Rosaria Bassi
Paola Giussani
Viviana Anelli
Thomas Colleoni
Marco Pedrazzi
Mauro Patrone
Paola Viani
Bianca Sparatore
Edon Melloni
Laura Riboni
Publication date: 01-03-2008
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 1/2008
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-007-9488-y

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

HMGB1 as an autocrine stimulus in human T98G glioblastoma cells: role in cell growth and migration

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

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