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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Molecular Cancer 1/2012

Galectin-1, a gene preferentially expressed at the tumor margin, promotes glioblastoma cell invasion

Zeitschrift:
Molecular Cancer > Ausgabe 1/2012
Autoren:
L Gerard Toussaint III, Allan E Nilson, Jennie M Goble, Karla V Ballman, C David James, Florence Lefranc, Robert Kiss, Joon H Uhm
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1476-4598-11-32) contains supplementary material, which is available to authorized users.

Competing interests

None of the listed authors have competing interests related to the publication of this manscript.

Authors’ contributions

LGT and JHU conceived of the study and designed the assays. LGT performed tumor xenografting, cell culture, and laser capture microdissection. LGT, FL, and RK wrote and edited the manuscript. AN designed and performed all DNA vector construction and sequencing. JG performed tissue culture, western blots, invasion assays, and immunohistochemistry. KB led the microarray statistical analysis. CDJ created the orthotopic xenograft model and provided guidance on its use in this project. All authors read and approved the final manuscript.

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.
Zusatzmaterial
Additional file1: Figure S1. Galectin-1 staining correlates with patient survival. Using a tissue microarray created at Mayo Clinic, we stained glioblastoma samples from 34 separate patients using immunohistochemistry for galectin-1. A survival analysis revealed a trend towards shorter survival in those patients harboring galectin-1 positive tumors. (PDF 262 KB)
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Authors’ original file for figure 1
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Authors’ original file for figure 6
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Literatur
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