Role of key genetic mutations on increasing migration of brain cancer cells through confinement Loan Bui 1 & Sayem H. Bhuiyan 1 & Alissa Hendrick 1 & Cheng-Jen Chuong 1 & Young-tae Kim 1,2 # Springer Science+Business Media New York 2017 Abstract Uncontrolled invasive cancer cell migration is among the major challenges for the treatment and manage- ment of brain cancer. Although the genetic profiles of brain cancer cells have been well characterized, the relationship between the genetic mutations and the cells’ mobility has not been clearly understood. In this study, using microfluidic devices that provide a wide range of physical confinements from 20 × 5 μm 2 to 3 × 5 μm 2 in cross sections, we studied the effect of physical confinement on the migratory capacity of cell lines with different types of mutations. Human glioblas- toma and genetically modified mouse astrocytes were used. Human glioblastoma cells with EGFRvIII mutation were found to exhibit high degree of migratory capacity in narrow confinement. From mouse astrocytes, cells with triple muta- tions (p53-/- PTEN-/- BRAF) were found to exhibit the highest level of migratory capacity in narrow confinement compared to both double (p53-/- PTEN-/-) and single (p53-/-) mutant cells. Furthermore, when treating the triple mutant astrocytes with AZD-6244, an inhibitor of the RAF/ MEK/ERK pathway, we found significant reduction in migra- tion through the confined channels when compared to that of controls (83% decrease in 5 × 5 μm 2 and 86% in 3 × 5 μm 2 channels). Our data correlate genetic mutations from different cell lines to their motility in different degrees of confinement. Our results also suggest a potential therapeutic target such as BRAF oncogene for inhibition of brain cancer invasion. Keywords Brain cancer . Invasion . Genetic mutation . Migratory capacity . Physical confinement 1 Introduction Malignant brain tumors continue to be a major disease of morbidity and mortality in many individuals from children to adults (Deorah et al. 2006; Huse and Holland 2010). Glioblastoma multiforme (GBM) has been known to be one of the most aggressive brain tumors (WHO, grade IV astrocy- toma) with an approximate survival of 1 year following diag- nosis (Jafri et al. 2013; Kroes et al. 2000; Parsons et al. 2008). There are two categories of GBM: the primary that is consid- ered as the advanced cancer, and the secondary which in- cludes that developed from previous lower-grade tumors. With current treatment options, patients with either primary or secondary GBM encounter indistinguishably poor progno- sis (Ohgaki and Kleihues 2013; Parsons et al. 2008). Currently, most mutations and genomic aberrations of GBM have been well characterized. For example, primary GBM mainly carried PTEN and EGFR mutation whereas p53 mutation was more common in secondary GBM (Ohgaki and Kleihues 2013; Ohgaki and Kleihues 2007). Despite heterogeneity, these malignant cells share a common capability of spreading along various confined tracts such as vasculatures or white matter tracts. These cells infiltrate a large amount of brain tissue leading to a rapid mortality rate (Gritsenko et al. 2012; Templeton et al. 2008). Therefore, a clear understanding of the relationship between the tumor ge- netic alterations and their acquired mobility to infiltrate is crucial for both the identification of aggressive cells and the formulation of effective therapeutic regimens. In this paper, we presented novel designs in microfluidic device and results demonstrating their use in studying the * Young-tae Kim ykim@uta.edu 1 Department of Bioengineering, University of Texas at Arlington, 500 UTA Blvd ERB244, Arlington, TX 76010, USA 2 Department of Urology, UT Southwestern Medical Center, Dallas, TX, USA Biomed Microdevices (2017) 19:56 DOI 10.1007/s10544-017-0197-9