Differential Characterization of Temozolomide-Resistant Human Glioma Cells.

Sheng-Wei Lai,Cheng-Fang Tsai,Chun-Chuan Chen,Hsiao-Yun Lin,Chingju Lin,Yu-Shu Liu,Dah-Yuu Lu,Bor-Ren Huang

doi:10.3390/ijms19010127

Abstract

Glioblastoma multiforme (GBM) is the most common type of primary and malignant tumor occurring in the adult central nervous system. Temozolomide (TMZ) has been considered to be one of the most effective chemotherapeutic agents to prolong the survival of patients with glioblastoma. Many glioma cells develop drug-resistance against TMZ that is mediated by increasing O-6-methylguanine-DNA methyltransferase (MGMT) levels. The expression of connexin 43 was increased in the resistant U251 subline compared with the parental U251 cells. The expression of epithelial–mesenchymal transition (EMT)-associated regulators, including vimentin, N-cadherin, and β-catenin, was reduced in the resistant U251 subline. In addition, the resistant U251 subline exhibited decreased cell migratory activity and monocyte adhesion ability compared to the parental U251 cells. Furthermore, the resistant U251 subline also expressed lower levels of vascular cell adhesion molecule (VCAM)-1 after treatment with recombinant tumor necrosis factor (TNF)-α. These findings suggest differential characteristics in the drug-resistant GBM from the parental glioma cells.

Highlights

Glioblastoma multiforme (GBM) is the most common primary brain tumor that affects the central nervous system in adults and is one of the deadliest cancers in humans [1]
methylguanine-DNA methyltransferase (MGMT) and Connexin 43 (Cx43) Are Upregulated in the TMZ-Resistant U251 Cells 2.1
The present study demonstrated that vascular cell adhesion molecule (VCAM)-1 expression was induced in GBM treated with tumor necrosis factor (TNF)-α, which subsequently promoted the interaction between monocytes and GBM

Summary

Introduction

Glioblastoma multiforme (GBM) is the most common primary brain tumor that affects the central nervous system in adults and is one of the deadliest cancers in humans [1]. Some studies have shown that Cx43 is downregulated in high-grade brain tumors [10,11], while others have demonstrated that an increased level of Cx43 is capable of conferring chemotherapeutic resistance to human glioma cells through the upregulation molecular mechanisms [12,13]. Overall, this reflects the lack of consensus for the pro- or anti-tumorigenic role for connexins in GBM

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Conclusion