TY - JOUR
T1 - Quantification of glioblastoma progression in zebrafish xenografts
T2 - Adhesion to laminin alpha 5 promotes glioblastoma microtumor formation and inhibits cell invasion
AU - Gamble, John T.
AU - Reed-Harris, Yuriyah
AU - Barton, Carrie L.
AU - La Du, Jane
AU - Tanguay, Robert
AU - Greenwood, Juliet A.
N1 - Funding Information:
We would like to thank Annie-Marie Girard-Pohjanpelto from the Center for Genome Research and Biocomputing at Oregon State University for her help in confocal training and imaging advice. We are grateful to the Sinnhuber Aquatic Research Laboratory for providing access to molecular biology equipment, supplies and zebrafish husbandry. Our work was supported in part by NSF grant 1310657 and NIH grant P30 ES000210.
Funding Information:
We would like to thank Annie-Marie Girard-Pohjanpelto from the Center for Genome Research and Biocomputing at Oregon State University for her help in confocal training and imaging advice. We are grateful to the Sinnhuber Aquatic Research Laboratory for providing access to molecular biology equipment, supplies and zebrafish husbandry. Our work was supported in part by NSF grant 1310657 and NIH grant P30 ES000210 .
Publisher Copyright:
© 2018 The Authors
PY - 2018/12/2
Y1 - 2018/12/2
N2 - 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.
AB - 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.
KW - Glioblastoma
KW - ImageJ
KW - Invasion
KW - Lama5
KW - Laminin alpha 5
KW - Zebrafish
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U2 - 10.1016/j.bbrc.2018.10.076
DO - 10.1016/j.bbrc.2018.10.076
M3 - Article
C2 - 30389143
AN - SCOPUS:85056803070
SN - 0006-291X
VL - 506
SP - 833
EP - 839
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -