title: Galectin-1, a gene preferentially expressed at the tumor margin, promotes glioblastoma cell invasion.
abstract: 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.
authors.affiliation: The Texas Brain and Spine Institute, Bryan, TX 77807, USA. Gtoussaint@medicine.tamhsc.edu
authors.forename: L Gerard
authors.initials: LG
authors.lastname: Toussaint
authors.forename: Allan E
authors.initials: AE
authors.lastname: Nilson
authors.forename: Jennie M
authors.initials: JM
authors.lastname: Goble
authors.forename: Karla V
authors.initials: KV
authors.lastname: Ballman
authors.forename: C David
authors.initials: CD
authors.lastname: James
authors.forename: Florence
authors.initials: F
authors.lastname: Lefranc
authors.forename: Robert
authors.initials: R
authors.lastname: Kiss
authors.forename: Joon H
authors.initials: JH
authors.lastname: Uhm
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D005109:Extracellular Matrix / Q000378:metabolism; D037483:Galectin 1 / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics; D014183:Transplantation, Heterologous
chemical_list: D037483:Galectin 1