한빛사 논문
Eun-Jung Lim1,13†, Seungmo Kim1†, Yoonjee Oh3, Yongjoon Suh1, Neha Kaushik1, Ji-Hyun Lee2, Hae-June Lee4, Min-Jung Kim5, Myung-Jin Park6, Rae-Kwon Kim7, Junghwa Cha3,12, Se Hoon Kim8, Jin-Kyoung Shim2, Junjeong Choi9, Jong Hee Chang2, Yong Kil Hong10, Yong Min Huh11, Pilnam Kim3,12*, Seok-Gu Kang2*, Su-Jae Lee1*
1Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Korea
2Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea
3Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea
4Division of Radiation Effect, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Korea
5Laboratory of Radiation Exposure & Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Korea
6Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Korea
7Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, Daejeon 34057, Korea
8Department of Pathology, Severance Hospital, Yonsei University, College of Medicine, Seoul 03722, Korea
9College of Pharmacy, Yonsei Institute of Pharmaceutical Science, Yonsei University, Incheon 21983, Korea
10Department of Neurosurgery, Seoul St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Seoul 06591, Korea
11Department of Radiology, Severance Hospital, Yonsei University, College of Medicine, Seoul 03722, Korea
12KAIST Institute for Health Science and Technology, Daejeon 34141, Korea
13Memorial Sloan Kettering, Cancer Center, New York, New York
†E.J. Lim and S. Kim contributed equally to this work.
*Corresponding author
Abstract
Background
Mesenchymal stem-like cells (MSLCs) have been detected in many types of cancer including brain tumors and have received attention as stromal cells in the tumor microenvironment. However, the cellular mechanisms underlying their participation in cancer progression remain largely unexplored. The aim of this study was to determine whether MSLCs have tumorigenic role in brain tumors.
Methods
To figure out molecular and cellular mechanisms in glioma invasion, we have been cultured glioma with MSLCs in co-culture system.
Results
Here, we show that MSLCs in human glioblastoma (GBM) secrete complement component C5a, which is known for its role as a complement factor. MSLC-secreted C5a increases ZEB1 expression via activation of p38 MAPK in GBM cells, thereby enhancing the invasion of GBM cells into parenchymal brain tissue.
Discussion
Our results reveal a mechanism by which MSLCs undergo crosstalk with GBM cells through the C5a/p38 MAPK/ZEB1 signaling loop and act as a booster in GBM progression.
Importance of Study
MSLCs activate p38 MAPK-ZEB1 signaling in GBM cells through the C5a in a paracrine manner, thereby boosting the invasiveness of GBM cells in the tumor microenvironment.
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