38P - Mena INV: A prospective bio-marker of glioma under hypoxia

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Central Nervous System Malignancies
Translational Research
Presenter Mohita Bhagat
Citation Annals of Oncology (2016) 27 (suppl_9): ix9-ix18. 10.1093/annonc/mdw574
Authors M. Bhagat
  • Biochemistry, All India Institute of Medical Sciences, 110029 - Delhi/IN

Abstract

Background

Mena, an actin regulatory gene, was found to be upregulated in several human cancers. Differential splicing of the Mena reports a 19 amino residue after the EVH1 domain producing a Mena invasion isoform (Menainv/Mena+++). Hypoxic regions are a predominant feature of growing tumors. In glioma, hypoxia activates multiple signaling pathways leading to angiogenesis and enhanced motility/invasion. These reports and the proposed role of Mena in regulating invasion and metastasis, prompted us to look into the expression pattern of total Mena (Pan Mena) and the INV variant (Mena INV) in gliomas under normoxic (20% O2) and hypoxic (0. 2% O2) conditions.

Methods

In order to delineate molecular crosstalk among factors driving glioma progression, we used knockdown and overexpression strategies followed by expression analysis by Q-PCR, immunofluorescence and western blot. Migratory potential of cells was assessed by migration assay.

Results

Hypoxic treatment exhibited a significant increase in expression levels of Mena INV in U87MG and A172 (Grade IV) glioma cells. In concordance with Mena INV expression, 0.2% O2 concentration exhibited a maximal effect on migration of glioma cells. On the contrary, hypoxic treatment did not induce Mena INV in Grade II cell lines –SW1088 and Gos-3, while Mena INV variant was totally absent in normal astrocytes. U87MG and A172 when separated into migrated and non-migrated cell populations, a drastic increase in Mena INV expression was observed in the migrated cell population. HIF-2α knockdown and overexpression, and not HIF-1α, affected Mena INV expression in a concomitant manner, indicating the effect of hypoxia on Mena INV via HIF-2α. Finally, significant positive correlation was obtained between HIF-2α and Mena INV in Glioblastoma patient samples.

Conclusions

The results indicate a role of Mena INV as a diagnostic marker to assess the migratory potential of transformed cells. We identify hypoxia as one of the reasons leading to increased migratory capabilities in transformed cell. This may increase the efficacy of successful local spread and metastasis, making tumor cells more aggressive.

Clinical trial indentification

Legal entity responsible for the study

Department of Biotechnology, India

Funding

Department of Biotechnology, India and University Grants Commission

Disclosure

All authors have declared no conflicts of interest.