**Author details**

require tumor cells to shrink and squeeze through tight interstitial space [40]. Cell shrinkage

the invasion potential of glioma cells (under publication). The role of BKCa channels in cell migration was already described [43]. The changes in proliferation and migration of cells over-expressing *KCNMA1v* were mostly attributed to increased levels of *KCNMA1* and BKCa channel protein expression in transfected cells. Additionally, overexpression of *KCNMA1v* in glioma cells may assist them to diffusely invade the normal brain. Due to this phenomenon, GBM patients typically show high propensity to recur as the cancer cells expressing *KCNMA1v* might survive surgical and therapeutic treatment. The xenograft tumors in mice likewise demonstrated increased growth, which correlated well with Ki-67 expression (under publication). The overexpression of *KCNMA1v* resulted in increased angiogenesis in the tumor xenografts, supporting the angiogenic role of *KCNMA1v*. The observation that the overexpression of *KCNMA1v* in human gliomas correlates with increased angiogenesis in high-grade gliomas further supports that *KCNMA1* splicing event is an important biological process for glioma progression. Consistent with this observation, we found that glioma cells over-expressing *KCNMA1v* secreted significantly the high level of angiogenic factor VEGF

Further investigation into the mechanisms and cellular events caused by *KCNMA1* splicing may lead to the development of future therapies for this highly deadly disease. Splice variants that are found in high-grade gliomas have clear diagnostic and prognostic values besides providing potential targets for anticancer drug development. Clinical outcome of *KCNMA1v* expression in high-grade glioma is expected to reveal the variants' clinical importance. This analysis is being performed in our laboratory. In conclusion, the results presented here might suggest that quantifying the levels of *KCNMA1v* could be useful to identify biological process that increases the malignancy and affect prognosis of high-grade

The authors thank the Scintilla Group, Bangalore, India; Anderson Cancer Institute and Mercer University Medical Center, Savannah, GA, USA; Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; Cedars-Sinai Medical Center, Los Angeles, CA, USA; American Cancer Society, USA; Georgia Cancer Coalition, Atlanta, GA, USA; and NIH for providing opportunity and research grant support. We also thank Dr. Nagendra of MVIT, Bangalore, for assisting us with the STRING software for the analysis and Michigan State University Research Center, Grand Rapids, MI, USA, for generating KKEG pathway using Affymetrix

efflux [42]. Consistent with these findings, the overexpression of *KCNMA1v* increased

ions [41], and BKCa channels may serve as pathway for regu-

requires the efflux of K<sup>+</sup>

(under publication).

**6. Conclusion**

glioma patients.

analysis data.

**Acknowledgements**

lated K<sup>+</sup>

234 Brain Tumors - An Update

and Cl<sup>−</sup>

Divya Khaitan1,2, Nagendra Ningaraj2,3,4\* and Lincy B. Joshua5

\*Address all correspondence to: sainagendra50@gmail.com

1 Department of Molecular Oncology, Scintilla Academy for Applied Sciences' Education and Research, Bangalore, India

2 Molecular Diagnostics, Scintilla Bio-MARC, BGS-BioMedical Research Institute, Bangalore, India

3 BGS-BioMedical Research Institute, Bangalore, India

4 BGS-Global Institute of Medical Sciences, Bangalore, India

5 BGS-Global Institute of Medical Sciences, Bangalore, India
