Cell migration in paediatric glioma; characterisation and potential therapeutic targeting

J. V. Cockle, S. Picton, J. Levesley, E. Ilett, A. M. Carcaboso, S. Short, L. P. Steel, A. Melcher, S. E. Lawler, A. Brüning-Richardson

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background:Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are highly aggressive brain tumours. Their invasive phenotype contributes to their limited therapeutic response, and novel treatments that block brain tumour invasion are needed.Methods:Here, we examine the migratory characteristics and treatment effect of small molecule glycogen synthase kinase-3 inhibitors, lithium chloride (LiCl) and the indirubin derivative 6-bromoindirubin-oxime (BIO), previously shown to inhibit the migration of adult glioma cells, on two pHGG cell lines (SF188 and KNS42) and one patient-derived DIPG line (HSJD-DIPG-007) using 2D (transwell membrane, immunofluorescence, live cell imaging) and 3D (migration on nanofibre plates and spheroid invasion in collagen) assays.Results:All lines were migratory, but there were differences in morphology and migration rates. Both LiCl and BIO reduced migration and instigated cytoskeletal rearrangement of stress fibres and focal adhesions when viewed by immunofluorescence. In the presence of drugs, loss of polarity and differences in cellular movement were observed by live cell imaging.Conclusions:Ours is the first study to demonstrate that it is possible to pharmacologically target migration of paediatric glioma in vitro using LiCl and BIO, and we conclude that these agents and their derivatives warrant further preclinical investigation as potential anti-migratory therapeutics for these devastating tumours.

Original languageEnglish
Pages (from-to)693-703
Number of pages11
JournalBritish Journal of Cancer
Volume112
Issue number4
Early online date27 Jan 2015
DOIs
Publication statusPublished - 17 Feb 2015
Externally publishedYes

Fingerprint

Glioma
Cell Movement
Pediatrics
Lithium Chloride
Oximes
Brain Neoplasms
Therapeutics
Fluorescent Antibody Technique
Nanofibers
Glycogen Synthase Kinase 3
Stress Fibers
Focal Adhesions
Collagen
Phenotype
Cell Line
Membranes
Pharmaceutical Preparations
Neoplasms

Cite this

Cockle, J. V. ; Picton, S. ; Levesley, J. ; Ilett, E. ; Carcaboso, A. M. ; Short, S. ; Steel, L. P. ; Melcher, A. ; Lawler, S. E. ; Brüning-Richardson, A. / Cell migration in paediatric glioma; characterisation and potential therapeutic targeting. In: British Journal of Cancer. 2015 ; Vol. 112, No. 4. pp. 693-703.
@article{63aa7057d1b8434a8613215c34d59078,
title = "Cell migration in paediatric glioma; characterisation and potential therapeutic targeting",
abstract = "Background:Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are highly aggressive brain tumours. Their invasive phenotype contributes to their limited therapeutic response, and novel treatments that block brain tumour invasion are needed.Methods:Here, we examine the migratory characteristics and treatment effect of small molecule glycogen synthase kinase-3 inhibitors, lithium chloride (LiCl) and the indirubin derivative 6-bromoindirubin-oxime (BIO), previously shown to inhibit the migration of adult glioma cells, on two pHGG cell lines (SF188 and KNS42) and one patient-derived DIPG line (HSJD-DIPG-007) using 2D (transwell membrane, immunofluorescence, live cell imaging) and 3D (migration on nanofibre plates and spheroid invasion in collagen) assays.Results:All lines were migratory, but there were differences in morphology and migration rates. Both LiCl and BIO reduced migration and instigated cytoskeletal rearrangement of stress fibres and focal adhesions when viewed by immunofluorescence. In the presence of drugs, loss of polarity and differences in cellular movement were observed by live cell imaging.Conclusions:Ours is the first study to demonstrate that it is possible to pharmacologically target migration of paediatric glioma in vitro using LiCl and BIO, and we conclude that these agents and their derivatives warrant further preclinical investigation as potential anti-migratory therapeutics for these devastating tumours.",
keywords = "DIPG, indirubin, lithium, migration, Paediatric high grade glioma",
author = "Cockle, {J. V.} and S. Picton and J. Levesley and E. Ilett and Carcaboso, {A. M.} and S. Short and Steel, {L. P.} and A. Melcher and Lawler, {S. E.} and A. Br{\"u}ning-Richardson",
year = "2015",
month = "2",
day = "17",
doi = "10.1038/bjc.2015.16",
language = "English",
volume = "112",
pages = "693--703",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "4",

}

Cockle, JV, Picton, S, Levesley, J, Ilett, E, Carcaboso, AM, Short, S, Steel, LP, Melcher, A, Lawler, SE & Brüning-Richardson, A 2015, 'Cell migration in paediatric glioma; characterisation and potential therapeutic targeting', British Journal of Cancer, vol. 112, no. 4, pp. 693-703. https://doi.org/10.1038/bjc.2015.16

Cell migration in paediatric glioma; characterisation and potential therapeutic targeting. / Cockle, J. V.; Picton, S.; Levesley, J.; Ilett, E.; Carcaboso, A. M.; Short, S.; Steel, L. P.; Melcher, A.; Lawler, S. E.; Brüning-Richardson, A.

In: British Journal of Cancer, Vol. 112, No. 4, 17.02.2015, p. 693-703.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cell migration in paediatric glioma; characterisation and potential therapeutic targeting

AU - Cockle, J. V.

AU - Picton, S.

AU - Levesley, J.

AU - Ilett, E.

AU - Carcaboso, A. M.

AU - Short, S.

AU - Steel, L. P.

AU - Melcher, A.

AU - Lawler, S. E.

AU - Brüning-Richardson, A.

PY - 2015/2/17

Y1 - 2015/2/17

N2 - Background:Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are highly aggressive brain tumours. Their invasive phenotype contributes to their limited therapeutic response, and novel treatments that block brain tumour invasion are needed.Methods:Here, we examine the migratory characteristics and treatment effect of small molecule glycogen synthase kinase-3 inhibitors, lithium chloride (LiCl) and the indirubin derivative 6-bromoindirubin-oxime (BIO), previously shown to inhibit the migration of adult glioma cells, on two pHGG cell lines (SF188 and KNS42) and one patient-derived DIPG line (HSJD-DIPG-007) using 2D (transwell membrane, immunofluorescence, live cell imaging) and 3D (migration on nanofibre plates and spheroid invasion in collagen) assays.Results:All lines were migratory, but there were differences in morphology and migration rates. Both LiCl and BIO reduced migration and instigated cytoskeletal rearrangement of stress fibres and focal adhesions when viewed by immunofluorescence. In the presence of drugs, loss of polarity and differences in cellular movement were observed by live cell imaging.Conclusions:Ours is the first study to demonstrate that it is possible to pharmacologically target migration of paediatric glioma in vitro using LiCl and BIO, and we conclude that these agents and their derivatives warrant further preclinical investigation as potential anti-migratory therapeutics for these devastating tumours.

AB - Background:Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are highly aggressive brain tumours. Their invasive phenotype contributes to their limited therapeutic response, and novel treatments that block brain tumour invasion are needed.Methods:Here, we examine the migratory characteristics and treatment effect of small molecule glycogen synthase kinase-3 inhibitors, lithium chloride (LiCl) and the indirubin derivative 6-bromoindirubin-oxime (BIO), previously shown to inhibit the migration of adult glioma cells, on two pHGG cell lines (SF188 and KNS42) and one patient-derived DIPG line (HSJD-DIPG-007) using 2D (transwell membrane, immunofluorescence, live cell imaging) and 3D (migration on nanofibre plates and spheroid invasion in collagen) assays.Results:All lines were migratory, but there were differences in morphology and migration rates. Both LiCl and BIO reduced migration and instigated cytoskeletal rearrangement of stress fibres and focal adhesions when viewed by immunofluorescence. In the presence of drugs, loss of polarity and differences in cellular movement were observed by live cell imaging.Conclusions:Ours is the first study to demonstrate that it is possible to pharmacologically target migration of paediatric glioma in vitro using LiCl and BIO, and we conclude that these agents and their derivatives warrant further preclinical investigation as potential anti-migratory therapeutics for these devastating tumours.

KW - DIPG

KW - indirubin

KW - lithium

KW - migration

KW - Paediatric high grade glioma

UR - http://www.scopus.com/inward/record.url?scp=84923611834&partnerID=8YFLogxK

U2 - 10.1038/bjc.2015.16

DO - 10.1038/bjc.2015.16

M3 - Article

VL - 112

SP - 693

EP - 703

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 4

ER -

Cockle JV, Picton S, Levesley J, Ilett E, Carcaboso AM, Short S et al. Cell migration in paediatric glioma; characterisation and potential therapeutic targeting. British Journal of Cancer. 2015 Feb 17;112(4):693-703. https://doi.org/10.1038/bjc.2015.16