Long-range and short-range tumor-stroma networks synergistically contribute to tumor-associated epilepsy

// Xiao-Yuan Mao 1,2 , Tursonjan Tokay 3 , Hong-Hao Zhou 1,2 and Wei-Lin Jin 4,5 1 Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, P. R. China 2 Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, P. R. China 3 Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, Republic of Kazakhstan 4 Institute of Nano Biomedicine and Engineering, Department of Instrument Science and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of Ministry of Education, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University, Shanghai, P. R. China 5 National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, P. R. China Correspondence to: Xiao-Yuan Mao, email: // Wei-Lin Jin, email: // Keywords : brain tumor, tumor microenvironment, tumor-associated epilepsy, long-range mode, short-range mode Received : December 07, 2015 Accepted : February 23, 2016 Published : March 07, 2016 Abstract Epileptic seizures are frequently caused by brain tumors. Traditional anti-epileptic treatments do not acquire satisfactory responses. Preoperative and postoperative seizures seriously influence the quality of life of patients. Thus, tumor-associated epilepsy (TAE) is an important subject of the current research. The delineation of the etiology of epileptogenesis in patients with primary brain tumor may help to find the novel and effective drug targets for treating this disease. In this review, we describe the current status of treatment of TAE. More importantly, we focus on the factors that are involved in the functional connectivity between tumors and stromal cells. We propose that there exist two modes, namely, long-range and short-range modes, which likely trigger neuronal hyperexcitation and subsequent epileptic seizures. The long-range mode is referred to as factors released by tumors including glutamate and GABA, binding to the corresponding receptor on the cellular membrane and causing neuronal hyperactivity, while the short-range mode is considered to involve direct intracellular communication between tumor cells and stromas. Gap junctions and tunneling nanotube network are involved in cellular interconnections. Future investigations focused on those two modes may find a potential novel therapeutic target for treating TAE.