TY - JOUR
T1 - Galectin-1, a gene preferentially expressed at the tumor margin, promotes glioblastoma cell invasion
AU - Toussaint, L. G.
AU - Nilson, Allan E.
AU - Goble, Jennie M.
AU - Ballman, Karla V.
AU - James, C. D.
AU - Lefranc, Florence
AU - Kiss, Robert
AU - Uhm, Joon H.
N1 - Funding Information:
We greatly appreciate the assistance of Alexey Leontovich and others at the Mayo Clinic Genomic Center Microarray Shared Resource. Bruce Morlan provided expert statistical assistance. Brett Carlson and Mark Schroeder instructed and provided assistance with tumor xenografting. In addition, we are indebted to Chris Lipinski for his help with radial migration assays. Reagents used in preliminary pilot assays were kindly provided by Yoel Kloog and Adrienne Cox. This work was supported by grants from the Sontag Foundation Distinguished Scientist Award (JHU), the NIH NRSA T32 NS 07494 (LGT) grant, the NIH LRP (LGT) grant, and the Mayo Clinic Clinician Investigator Training Program (LGT).
PY - 2012/5/14
Y1 - 2012/5/14
N2 - Background: High-grade gliomas, including glioblastomas (GBMs), are recalcitrant to local therapy in part because of their ability to invade the normal brain parenchyma surrounding these tumors. Animal models capable of recapitulating glioblastoma invasion may help identify mediators of this aggressive phenotype.Methods: Patient-derived glioblastoma lines have been propagated in our laboratories and orthotopically xenografted into the brains of immunocompromized mice. Invasive cells at the tumor periphery were isolated using laser capture microdissection. The mRNA expression profile of these cells was compared to expression at the tumor core, using normal mouse brain to control for host contamination. Galectin-1, a target identified by screening the resulting data, was stably over-expressed in the U87MG cell line. Sub-clones were assayed for attachment, proliferation, migration, invasion, and in vivo tumor phenotype.Results: Expression microarray data identified galectin-1 as the most potent marker (p-value 4.0 x 10-8) to identify GBM cells between tumor-brain interface as compared to the tumor core. Over-expression of galectin-1 enhanced migration and invasion in vitro. In vivo, tumors expressing high galectin-1 levels showed enhanced invasion and decreased host survival.Conclusions: In conclusion, cells at the margin of glioblastoma, in comparison to tumor core cells, have enhanced expression of mediators of invasion. Galectin-1 is likely one such mediator. Previous studies, along with the current one, have proven galectin-1 to be important in the migration and invasion of glioblastoma cells, in GBM neoangiogenesis, and also, potentially, in GBM immune privilege. Targeting this molecule may offer clinical improvement to the current standard of glioblastoma therapy, i.e. radiation, temozolomide, anti-angiogenic therapy, and vaccinotherapy.
AB - Background: High-grade gliomas, including glioblastomas (GBMs), are recalcitrant to local therapy in part because of their ability to invade the normal brain parenchyma surrounding these tumors. Animal models capable of recapitulating glioblastoma invasion may help identify mediators of this aggressive phenotype.Methods: Patient-derived glioblastoma lines have been propagated in our laboratories and orthotopically xenografted into the brains of immunocompromized mice. Invasive cells at the tumor periphery were isolated using laser capture microdissection. The mRNA expression profile of these cells was compared to expression at the tumor core, using normal mouse brain to control for host contamination. Galectin-1, a target identified by screening the resulting data, was stably over-expressed in the U87MG cell line. Sub-clones were assayed for attachment, proliferation, migration, invasion, and in vivo tumor phenotype.Results: Expression microarray data identified galectin-1 as the most potent marker (p-value 4.0 x 10-8) to identify GBM cells between tumor-brain interface as compared to the tumor core. Over-expression of galectin-1 enhanced migration and invasion in vitro. In vivo, tumors expressing high galectin-1 levels showed enhanced invasion and decreased host survival.Conclusions: In conclusion, cells at the margin of glioblastoma, in comparison to tumor core cells, have enhanced expression of mediators of invasion. Galectin-1 is likely one such mediator. Previous studies, along with the current one, have proven galectin-1 to be important in the migration and invasion of glioblastoma cells, in GBM neoangiogenesis, and also, potentially, in GBM immune privilege. Targeting this molecule may offer clinical improvement to the current standard of glioblastoma therapy, i.e. radiation, temozolomide, anti-angiogenic therapy, and vaccinotherapy.
KW - Galectin-1
KW - Glioblastoma
KW - Invasion
KW - Migration
KW - Proliferation
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U2 - 10.1186/1476-4598-11-32
DO - 10.1186/1476-4598-11-32
M3 - Article
C2 - 22583806
AN - SCOPUS:84860801440
SN - 1476-4598
VL - 11
JO - Molecular cancer
JF - Molecular cancer
M1 - 32
ER -