PUBLICATION

Quantification of glioblastoma progression in zebrafish xenografts: Adhesion to laminin alpha 5 promotes glioblastoma microtumor formation and inhibits cell invasion

Authors
Gamble, J.T., Reed-Harris, Y., Barton, C.L., La Du, J., Tanguay, R., Greenwood, J.A.
ID
ZDB-PUB-181106-2
Date
2018
Source
Biochemical and Biophysical Research Communications   506(4): 833-839 (Journal)
Registered Authors
Barton, Carrie, La Du, Jane K., Tanguay, Robyn L.
Keywords
Glioblastoma, ImageJ, Invasion, Lama5, Laminin alpha 5, Zebrafish
MeSH Terms
  • Neoplasm Invasiveness
  • Glioblastoma/metabolism*
  • Glioblastoma/pathology*
  • Morpholinos/pharmacology
  • Cell Line, Tumor
  • Humans
  • Animals
  • Disease Progression*
  • Xenograft Model Antitumor Assays*
  • Gene Knockdown Techniques
  • Brain Neoplasms/metabolism*
  • Brain Neoplasms/pathology*
  • Zebrafish/metabolism*
  • Tumor Microenvironment/drug effects
  • Laminin/metabolism*
(all 15)
PubMed
30389143 Full text @ Biochem. Biophys. Res. Commun.
Abstract
Glioblastoma (GBM) is a deadly disease due to its ability to quickly invade and destroy brain tissue. Slowing or stopping GBM cell progression is crucial to help those inflicted with the disease. Our lab created an embryo-larval zebrafish xenograft model as a tool to study human GBM progression in an observable brain environment. The zebrafish brain is a dynamic and complex environment providing an optimal setting for studying GBM cell progression. Here we demonstrate the ability of our model to quantitate GBM proliferation, dispersal, blood vessel association, microtumor formation, and individual cell invasion by evaluating the importance of an extracellular matrix protein, laminin alpha 5 (lama5), on U251MG cell progression. Lama5 has been implicated in cancer cell survival, proliferation and invasion and is a known adhesion site for GBM cells. While lama5 is highly expressed in endothelial cells in the brain, it is unknown how lama5 affects GBM behavior. Using a lama5 morpholino, we discovered that lama5 decreased U251MG dispersal by 23% and doubles the formation of blood vessel dependent microtumors. Despite lama5 being a known attachment site for GBM, lama5 expression had no effect on U251MG association with blood vessels. Analysis of individual U251MG cells revealed lama5 significantly lowered invasion as mobile U251MG cells traveled 32.5  μm less, invaded 5.0 μm/hr slower and initiated invasion 60% few times per cell.
Genes / Markers
Figures
Figure Gallery (3 images)
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
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Human Disease / Model
No data available
Sequence Targeting Reagents
Target Reagent Reagent Type
lama5MO3-lama5MRPHLNO
1 - 1 of 1
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Fish
No data available
Antibodies
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Orthology
No data available
Engineered Foreign Genes
No data available
Mapping
No data available
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Citation
Gamble, J.T., Reed-Harris, Y., Barton, C.L., La Du, J., Tanguay, R., Greenwood, J.A. (2018) Quantification of glioblastoma progression in zebrafish xenografts: Adhesion to laminin alpha 5 promotes glioblastoma microtumor formation and inhibits cell invasion. Biochemical and Biophysical Research Communications. 506(4):833-839.