Crosstalk between GBM cells and mesenchymal stemlike cells promotes the invasiveness of GBM through the C5a/p38/ZEB1 axis

被引：48

作者：

Lim, Eun-Jung ^{[1
,13
]}

Kim, Seungmo ^{[1
]}

Oh, Yoonjee ^{[3
]}

Suh, Yongjoon ^{[1
]}

Kaushik, Neha ^{[1
]}

Lee, Ji-Hyun ^{[2
]}

Lee, Hae-June ^{[4
]}

Kim, Min-Jung ^{[5
]}

Park, Myung-Jin ^{[6
]}

Kim, Rae-Kwon ^{[7
]}

Cha, Junghwa ^{[3
,9
]}

Kim, Se Hoon ^{[8
]}

Shim, Jin-Kyoung ^{[2
]}

Choi, Junjeong ^{[12
]}

Chang, Jong Hee ^{[2
]}

Hong, Yong Kil ^{[10
]}

Huh, Yong Min ^{[11
]}

Kim, Pilnam ^{[3
,12
]}

Kang, Seok-Gu ^{[2
]}

Lee, Su-Jae ^{[1
]}

机构：

[1] Hanyang Univ, Res Inst Nat Sci, Dept Life Sci, Seoul, South Korea

[2] Yonsei Univ, Severance Hosp, BrainTumor Ctr, Dept Neurosurg,Coll Med, 50-1 Yonsei Ro, Seoul 03722, South Korea

[3] Korea Adv Inst Sci & Technol, Dept Bio & Brain Engn, Daejeon 34141, South Korea

[4] Korea Inst Radiol & Med Sci, Div Radiat Effect, Seoul, South Korea

[5] Korea Inst Radiol & Med Sci, Natl Radiat Emergency Med Ctr, Lab Radiat Exposure & Therapeut, Seoul, South Korea

[6] Korea Inst Radiol & Med Sci, Div Radiat Canc Biol, Seoul, South Korea

[7] Korea Atom Energy Res Inst, Dept Radiat Biol, Environm Radiat Res Grp, Daejeon, South Korea

[8] Yonsei Univ, Severance Hosp, Coll Med, Dept Pathol, Seoul, South Korea

[9] Yonsei Univ, Coll Pharm, Yonsei Inst Pharmaceut Sci, Incheon, South Korea

[10] Catholic Univ Korea, Dept Neurosurg, Coll Med, Seoul St Marys Hosp, Seoul, South Korea

[11] Yonsei Univ, Severance Hosp, Coll Med, Dept Radiol, Seoul, South Korea

[12] KAIST Inst Hlth Sci & Technol, Daejeon, South Korea

[13] Mem Sloan Kettering, Canc Ctr, New York, NY USA

来源：

NEURO-ONCOLOGY | 2020年 / 22卷 / 10期

基金：

新加坡国家研究基金会;

关键词：

C5a; glioblastoma; invasiveness; mesenchymal stem-like cells; tumor microenvironment; PREDICT PROGNOSIS; STROMAL CELLS; BRAIN-TUMOR; GLIOBLASTOMA; GROWTH; TEMOZOLOMIDE;

D O I：

10.1093/neuonc/noaa064

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background. Mesenchymal stemlike 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 a tumorigenic role in brain tumors. Methods. To figure out molecular and cellular mechanisms in glioma invasion, we have cultured glioma with MSLCs in a 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 expression of zinc finger E-box-binding homeobox 1 (ZEB1) via activation of p38 mitogen-activated protein kinase (MAPK) in GBM cells, thereby enhancing the invasion of GBM cells into parenchymal brain tissue. Conclusion. 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.

引用

页码：1452 / 1462

页数：11

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