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

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.

ATF4 promotes angiogenesis and neuronal cell death and confers ferroptosis in a xCT-dependent manner

“…These features promote angiogenesis and neuronal damage. 1 , 2 These stress conditions can, in principle, also affect tumor cells. However, tumor cells are able to withstand these factors and remain metabolically adapted under such toxic conditions.…”

Ferroptosis in glioma treatment: Current situation, prospects and drug applications

“…In addition, the growth-promoting effect of ATF4 on cells is mediated by xCT. P a t h o l o g i c a l v e s s e l s c o n s t i t u t e a t h e s p e c i fi c microenvironmental niche in primary brain tumors (121,122). The expression level of ATF4 affected the growth of tumor vessels; specifically, ATF4 overexpression increased the number and length of tumor vessels, and ATF4 knockdown led to the opposite effect (76).…”

Evaluación de polimorfismos en genes relacionados con la inflamación en pacientes mexicanos con epilepsia

“…Las convulsiones epilépticas a menudo pueden ser causadas por la presencia de tumores cerebrales y se ha demostrado que el microambiente tumoral es un factor importante para el desarrollo de la epilepsia (Conti et al, 2011). Se estima que la incidencia de convulsiones en pacientes con tumores cerebrales varía entre el 30% y el 100% dependiendo del tipo de tumor (Mao et al, 2016). A menudo se manifiestan como convulsiones focales con generalización secundaria y son refractarias al tratamiento antiepiléptico (Danfors et al, 2009).…”