Gong Weiyi, Wang Zhimin, Wan Yi, Shi Lei, Zhou Youxin
aDepartment of Neurosurgery, The First Affiliated Hospital of Soochow University bDepartment of Neurosurgery, The First People's Hospital of Kunshan Affiliated with Jiangsu University cDepartment of Neurosurgery, Suzhou Kowloon Hospital affiliated with Shanghai Jiao Tong University School of Medicine, Suzhou, People's Republic of China.
Neuroreport. 2014 May 28;25(8):625-32. doi: 10.1097/WNR.0000000000000161.
ABCG2 is a member of the ATP-binding cassette transporter family, which has been detected in a wide variety of human aggressive tumors, including glioma stem cells (GSCs), glioma tissues of higher grades, and implanted glioma xenografts. Previous research has implied that ABCG2 might be associated closely with invasion and spread in tumors. However, the specific roles and mechanisms of ABCG2 in regulating the migration and invasion of GSCs remain unclear. In this study, we aimed to identify the effects and mechanisms of ABCG2 on invasion by GSCs. Our results showed that downregulation of ABCG2 protein significantly inhibited the migration and invasion potentials of U251 GSCs. Further research on the underlying mechanism showed that the effects of ABCG2 downregulation on inhibiting the migration and invasion of U251 GSCs were through significantly decreasing the activity of matrix metalloproteinase-9, but not the expression of matrix metalloproteinase-9 protein. These findings show that ABCG2 plays an important role in regulating the migration and invasion of GSC, and represents a potential novel therapeutic agent to target the progression of GSCs.
ABCG2是ATP结合盒转运蛋白家族的一员,已在多种人类侵袭性肿瘤中被检测到,包括胶质瘤干细胞(GSCs)、高级别胶质瘤组织和植入的胶质瘤异种移植物。先前的研究表明,ABCG2可能与肿瘤的侵袭和扩散密切相关。然而,ABCG2在调节GSCs迁移和侵袭中的具体作用和机制仍不清楚。在本研究中,我们旨在确定ABCG2对GSCs侵袭的影响及其机制。我们的结果表明,ABCG2蛋白的下调显著抑制了U251 GSCs的迁移和侵袭能力。对潜在机制的进一步研究表明,ABCG2下调对抑制U251 GSCs迁移和侵袭的影响是通过显著降低基质金属蛋白酶-9的活性,而不是基质金属蛋白酶-9蛋白的表达。这些发现表明,ABCG2在调节GSCs的迁移和侵袭中起重要作用,并代表了一种潜在的新型治疗靶点,可用于靶向GSCs的进展。